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PubMed2005

Goblet cell carcinoid of the appendix.

BACKGROUND: Goblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management. METHODS: Published studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix. RESULTS: Based on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation. CONCLUSION: GCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination.

Journal Article↗

PubMed2000

The primate appendix: a reassessment.

The presence of a vermiform appendix is often cited as a shared, derived character uniting the Hominoidea (apes and humans). However, appendix-like structures have been reported for many other primate taxa. A review of the literature reveals that the confusion arises because several different, and sometimes contradictory, criteria are enlisted to distinguish an appendix. The measures most frequently used to define this structure are gross shape and certain aspects of histology (e.g., lymphoid concentration). Unfortunately, descriptions of shape lack quantification, and histological thin-sections have not been studied for many primate taxa. In addition, although lymphoid concentration in the human appendix is known to vary considerably with age, this information is rarely reported in the primate literature. Given these complications, additional studies on the morphology and ontogeny of this region are warranted. This research will lead to a more accurate definition of the vermiform appendix. Most authors currently describe this feature as a narrow diverticulum of the cecum with thick walls and concentrated lymphoid tissue. However, the presence of thick mucosal layers and appreciable lymphoid tissue in taxa lacking appendices (e. g., Saguinus, Cercocebus) suggests that these features may be primitive primate traits. If so, wall thickness and lymphoid concentration cannot be used to define the vermiform appendix. These results suggest that a more rigorous definition of the appendix is requisite for this feature to be used in primate systematics.

Animals↗

PubMed1994

The appendix functions as a mammalian bursal equivalent in the developing rabbit.

In this paper we present genomic DNA sequence and histological evidence that the appendix is a site of diversification of the rabbit's primary antibody repertoire. By 6 weeks after birth, the B cell follicular regions of the rabbit appendix and the distribution of the resident lymphoid cells bear a strong morphological resemblance to similar regions within two primary lymphoid tissues, the chicken bursa and the sheep ileal Peyer's patch. However, similarities between the rabbit appendix, chicken bursa and sheep ileal Peyer's patch end as these animals reach adulthood. The rabbit appendix undergoes morphological and cellular distribution changes as it matures taking on the appearance of a secondary lymphoid tissue, while the sheep ileal Peyer's patch and the chicken bursa both involute. We determined DNA sequences of PCR amplified rearranged variable region genes from germinal center B cells of 6 week old rabbits isolated from several different appendix dark zones and light zones. There was a trend toward a higher degree of diversification from the germ-line VH gene DNA sequence in dark zones than light zones. It is likely that both gene conversion and somatic hypermutation are responsible for the nucleotide changes we observed. Our findings suggest that the rabbit appendix functions as a mammalian bursal equivalent early in development. As the rabbit matures, the appendix appears to evolve into a secondary lymphoid tissue resembling secondary GALT in appearance and possibly in function.

Amino Acid Sequence↗

PubMed1983

Vermiform appendix located within the cecal wall. Anomalies and bizarre locations.

The unusual finding of an acute appendix located within the posterior wall of the cecum, beneath the serosa, and its surgical removal is described. In order to remove the appendix, the cecal wall had to be incised. The appendix had no serosal covering, and had the gross appearance of a peeled seedless grape. The anatomy and embryology of the vermiform appendix, including this aberration, are presented briefly. A discussion of the difficult-to-find appendix is presented. The possibility exists that some of the reported cases of agenesis of the appendix could have been an overlooked intracecal appendix.

Adolescent↗

PubMed2006

A neonate with an intact congenital umbilical appendix: an alternative theory on the etiology of the appendico-umbilical fistula.

Neonatal umbilical anomalies usually represent remains of the vitelline duct or the allantois. We describe a case of an umbilical appendix in a neonate. The vermiform appendix was found to be positioned in the umbilical cord. In a brief literature review we found eight other reports concerning umbilical appendices. In this article we describe a possible embryological explanation for the development of an umbilical appendix, and discuss whether or not the appendiceal umbilical fistulae reported are congenital or iatrogenic. The possible association between an umbilical appendix and different forms of malpositioning and rotation of the gut is also discussed. Protrusion of the neonatal appendix into the umbilical cord represents a different entity of congenital anomalies. It is important to realize that, in the case of an unrecognized umbilical appendix, medical procedures (e.g., canulation or clamping of the umbilicus) may produce an iatrogenic appendico-umbilical fistula. Careful inspection and palpation of the umbilical cord prior to these procedures may prevent a fistula being created. Furthermore, because the possible association between umbilical appendices and different kinds of malpositioning of the gut is so far not wholly elucidated, we recommend further (radiological) investigation in each case of an umbilical appendix. Correct positioning of the bowel needs to be confirmed in order to rule out possible future complications.

Appendectomy↗

PubMed2006

The appendix sign: a radiographic marker for irreducible intussusception.

PURPOSE: Radiographic reduction (hydrostatic or pneumatic) of intussusception has become the standard of care in the pediatric population with success rates of more than 80%. Identification of those patients who are likely to fail nonoperative management could lead to earlier operation, a reduction in radiation exposure, and a decreased risk for complications after repeated attempts at enema reduction. During successful radiographic reduction, the small bowel is almost always visualized before the appendix. Visualization of the appendix before visualization of the small bowel during a successful reduction of an intussusception is a rare event. We report a new radiographic sign that we have termed the appendix sign (radiographic visualization of the appendix without reflux of air or contrast into the small intestine), which we hypothesize may have association with failure of nonoperative management. METHOD: We performed a retrospective review of the last 12 years of irreducible intussusception. The associated studies were then reviewed to examine the incidence, sensitivity, and specificity of this radiographic finding. RESULTS: Ninety-one cases of intussusception were identified and had films available for review. Seventy-seven (76%) of the studies included the appropriate image. The appendix sign was visualized in 14 studies for an incidence of 18%. Of 14 patients, 10 failed enema reduction (positive predictive value, 71%). The sensitivity of the appendix sign is 43%. The specificity of the sign is 93%. CONCLUSIONS: Our experience suggests that the presence of an appendix sign is associated with failing enema reduction of an intussusception and may be useful as a marker for determining the end point for further attempts at radiographic reduction.

Appendix↗

PubMed2004

Interaction of pathogenic bacteria with rabbit appendix M cells: bacterial motility is a key feature in vivo.

Rabbit appendix consists mainly of lymphoid follicles (LF) covered by M cells, the specialized antigen-sampling cells of the mucosal immune system, and surrounded by glandular epithelium. Until now, these M cells have been characterized morphologically and histologically by using cellular markers. Here, the adhesion and transport of pathogenic bacteria were investigated to assess the function of M cells of the appendix. We used the enteroinvasive motile Salmonella typhimurium and the rabbit enteropathogenic non-motile Escherichia coli RDEC-1, which are known to target specifically rabbit M cells of Peyer's patches (PPs). We found that S. typhimurium efficiently attached and was transported through appendix M cells in vivo. In contrast to S. typhimurium, RDEC-1 targeted M cells only ex vivo, when bacteria were allowed to have direct contact with the surface of the follicle. The difference in interaction of the two bacteria with appendix M cells led us to investigate whether this could be correlated with the lack of motility of RDEC-1. We used an aflagellate mutant of S. typhimurium and found that it had the same infection phenotype as RDEC-1. Gene complementation restored the efficiency of infection to that of S. typhimurium wild-type strain. In conclusion, we show that M cells of the appendix display features of the canonical M cells of PP, since they efficiently sample luminal pathogenic bacteria. However, due to the morphology of the appendix, motile bacteria appear to be more potent in their interactions with appendix M cells.

Animals↗

PubMed2005

Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix.

Young rabbit appendix is a homologue of chicken bursa of Fabricius; both are crucial sites for preimmune B-cell repertoire diversification. Here, we report that appendix regulates precursor lymphocyte recruitment for further development by modulating the sites of extravasation. The total area of peripheral node addressin-positive (PNAd(+)) high endothelial venules (HEVs) increased from 1 day to 1 week after birth, remained constant up to 2 weeks and declined to a low and persistent amount by 3 weeks. In normal 1-week and manipulated 5-week appendix where growth of follicles was retarded, PNAd(+) HEVs were present in the basolateral sides of B-cell follicles whereas, in normal 5-wk-appendix these were restricted to T-cell areas. The PNAd was expressed on the lumenal surface of HEVs. The proportions of CD62L(+) B cells in appendix declined from approximately 40% at 3 days to 2-3% at 4 weeks. In lymphocyte transfer experiments, CD62L(+) B cells were preferentially recruited compared with CD62L(-) B cells, anti-PNAd antibody blocked migration of B cells by approximately 50%, and 100 times more B cells were recruited in 1-week compared to 6-week appendix. Thus, a unique spatiotemporal expression pattern of PNAd(+) HEVs is associated with development of B-cell follicles. This regulates migration of blood-borne B-lymphocytes into developing appendix by interacting with CD62L.

Animals↗

PubMed1997

[Ultrasonography of the normal vermiform appendix].

AIM: To study the detectability and the appearance of the vermiform appendix with ultrasound in asymptomatic adults. METHODS: A prospective study was performed on 300 patients, selected without regard to age, sex and weight. We tried to visualize the appendix with a 3.5 MHz annular array and a 5 MHz linear array transducer. RESULTS: In 63% of the patients the appendix was clearly visualised. The main reasons for non-visualisation were obesity with insufficient ultrasound penetration (38%) and the caecum laying in pelvic or atypical position (24%). In 31%, no cause was apparent but we assume that the appendix often lies behind the caecum. The sonographic image showed an aperistaltic target originating at the caecum, and ending blindly. In 42% of cases the appendix was ovoid in transverse section; in 32%, round; and in 26% both forms were found within one appendix. Intraluminal gas was visible in 86%. The mean transverse diameter was 5.2 mm (min. 3 mm, max. 13 mm) and in 76% the transverse diameter was lower than 6 mm. CONCLUSION: The sonographic detectability, the appearance and the size of the normal appendix show considerable variations.

Adult↗

PubMed1997

Urinary reconstruction using appendix as a urinary and catheterizable conduit in 12 patients.

BACKGROUND: The appendix vermiformis can provide an excellent urinary conduit or a catheterizable outlet in continent urinary reservoirs in selected cases. We report our clinical experience using the appendix in urinary reconstruction in adult patients. METHODS: A total of 12 patients underwent urinary reconstruction using the appendix. The indications were pelvic malignancies except for 1 patient with neurogenic bladder and difficulty in self-catheterization via urethra. The appendix was used as a catheterizable conduit in 8 patients, and as a urinary conduit in 4 patients. The in situ submucosally embedded method was used in 6 patients and the Mitrofanoff method was used in 2 patients. Follow-up ranged from 3 to 41 months (mean, 22). RESULTS: Early complications occurred in 3 patients (wound infection, false passage and intestinal anasotomotic leak). Late complications occurred in 3 (slight hydronephrosis, ileus, stomal stenosis). Emergent colostomy and pouchstomy with resection of the appendix was performed in the patient with anastomotic leak. The isoperistaltic Kock nipple valve was reconstructed for continence in this case. Prolonged ileus in 1 patient was treated by open surgery. Other complications were managed conservatively. End results were excellent in 8 patients, good in 3, and poor in 1. CONCLUSIONS: The appendix can be used advantageously as an outlet of continent urinary reservoirs or for a urinary conduit when the ureter is too short to reach the skin. Complete continence and easy catheterization can be obtained, and the appendix construction can be used as a urinary conduit instead of the ileal conduit in poor risk patients.

Aged↗

PubMed2002

Frequency of visualization and thickness of normal appendix at nonenhanced helical CT.

PURPOSE: To evaluate the frequency of visualization, thickness, and features of the normal appendix at nonenhanced helical computed tomography (CT). MATERIALS AND METHODS: Three radiologists blinded to patient surgical history retrospectively reviewed CT scans obtained for renal colic assessment in 187 consecutive patients. No contrast material was administered. The frequency of visualization and the two-wall thickness of normal appendices were recorded. Interobserver agreement and effect of adequacy of intraperitoneal fat on identification of the appendix were assessed. RESULTS: The prevalence of appendectomy was 10.7% (20 of 187 patients). The means for the three reviewers' sensitivity, specificity, positive and negative predictive values, and accuracy of visualization of normal appendix were 79% (CI: 73%, 84%), 90% (CI: 78%, 96%), 98% (CI: 97%, 99%), 34% (CI: 22%, 47%), and 80% (CI: 74%, 86%), respectively. There was no significant difference among the three reviewers (P >.05) according to conditional logistic regression and exact McNemar test results. For all reviewers, the frequency of appendix visualization was significantly lower in patients with less intraperitoneal fat (P =.01-.001, chi(2) test). The mean thickness of normal appendix if no intraluminal content was visualized was 6.6 mm +/- 1.0 (SD), and the mean thickness, excluding visualized intraluminal content, was 3.6 mm +/- 0.8. The nonweighted kappa value for interobserver agreement for normal appendix visualization was 0.69-0.75 among the three reviewers, which indicated good to excellent agreement. CONCLUSION: Most normal appendices are seen at nonenhanced helical CT. The thickness of normal appendix, when the content is not recognizable, overlaps the values currently used to diagnose appendicitis at CT.

Adolescent↗

PubMed2004

Appendix in children with cystic fibrosis: US features.

PURPOSE: To evaluate the ultrasonographic (US) appearance of the appendix in children with cystic fibrosis but who were asymptomatic for appendicitis. MATERIALS AND METHODS: Between March 2001 and March 2002, 31 children (14 boys, 17 girls; mean age, 9.5 years; range, 2-16 years) with cystic fibrosis underwent graded-compression US of the appendix. The recordings were analyzed in consensus by two radiologists specialized in US. The overall appendiceal diameter and change in diameter during graded compression, wall dimensions, contents of material in the lumen, and periappendicular fat were evaluated. The exclusion criterion was abdominal pain at the time of investigation. RESULTS: In all but one patient, the appendix was visualized with US. The diameter of the appendix ranged from 4.0 to 14.5 mm (mean, 8.3 mm). In 25 patients (83.3%), the appendix measured more than 6.0 mm. In six patients, the diameter of the appendix changed when graded compression was applied. Mucoid material was found in the lumen in 27 of 30 patients. No wall thickening occurred, and concentric layer structures of the wall were intact. No involvement of the neighboring mesenteric or omental fat was encountered. CONCLUSION: The appendiceal diameter was enlarged in the majority of children examined. The lumen contained mucoid contents. Therefore, the diameter of the appendix alone may not be a parameter for diagnosing appendicitis in patients with cystic fibrosis.

Adolescent↗

PubMed2006

Right lower quadrant pain: value of the nonvisualized appendix in patients at multidetector CT.

PURPOSE: To retrospectively determine the value of the nonvisualized appendix at multidetector computed tomography (CT) in patients with acute right lower quadrant pain in whom appendicitis was a consideration. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study, with waiver of informed consent. Records were retrospectively reviewed in patients who presented to the emergency department between April 29 and October 31, 2003, with right lower quadrant pain. Scanning was performed with the same eight-detector row CT scanner by using oral and (unless contraindicated) intravenous contrast agents, and transverse and coronal reformations were obtained. Two radiologists prospectively evaluated all scans at the time of the examination and rendered a consensus opinion. Clinical follow-up of at least 3 months' duration was performed retrospectively for patients whose appendix was not visualized to determine whether appendicitis had developed. Statistical analysis and calculation of percentages with confidence intervals (CIs) were performed. RESULTS: Of the 400 consecutive patients who underwent multidetector CT, 132 (33.0%) were male and 268 (67.0%) were female. Eighty patients (20.0%) had acute appendicitis and 79 (19.8%) had another cause for abdominal pain. A normal appendix with no other cause for pain was seen in 182 patients (45.5%). In 59 patients (14.8%), the appendix was not visualized. Of these 59 patients, 50 had adequate follow-up. Clinical follow-up was uneventful in 49 of these 50 patients. Thus, on otherwise normal multidetector CT scans in patients suspected of having acute appendicitis, nonvisualization of the appendix was negative for appendicitis in 98% (95% CI: 71%, 100%) of cases. Conversely, when the appendix was seen at multidetector CT and was abnormal, appendicitis was present in 95% (95% CI: 72%, 100%) of cases. CONCLUSION: In patients with right lower quadrant pain, a nonvisualized appendix at multidetector CT reliably excludes acute appendicitis.

Acute Disease↗

PubMed2003

Prepro-endothelin-1 mRNA and its mature peptide in human appendix.

Because the precise immunopathological events occurring in appendicitis are not completely understood, possible local production of endothelin-1 (ET-1) in human appendix was investigated. We used immunohistochemistry and in situ hybridization to detect the presence, distribution, and phenotype of ET-1-positive cells and prepro-ET-1 (pp-ET-1) mRNA-expressing cells. ET-1-positive stromal cells and pp-ET-1 mRNA-expressing cells were detected with different distributions and relative frequencies in normal control appendix, histologically normal appendix, and inflamed appendix. Six of 20 histologically normal appendixes from patients with a clinical diagnosis of acute appendicitis had many ET-1-positive stromal cells and high pp-ET-1 mRNA expression, similar to inflamed appendix. Forty percent of the pp-ET-1 mRNA-expressing cells were neutrophils, and the other positive cells were mast cells and macrophages. We suggest that local production of ET-1 by neutrophils and other inflammatory cells could be a molecular sign of focal inflammation in histologically normal appendixes and that ET-1 could be implicated, with other cytokines, in the pathogenesis of appendicitis by inducing appendiceal ischemia through vasoconstriction.

Appendicitis↗

PubMedDate not supplied

Mucinous cystadenoma of the appendix in a patient with systemic lupus erythematosus.

A 38-year-old female with systemic lupus erythematosus presented with abdominal pain, diarrhea and iron-deficient anemia. Computed tomogram showed a 2 x 4 cm inhomogeneous lesion of the right adnexa. An unusual mass was identified extending from the appendiceal orifice at colonoscopy, and an 8 cm tubular appendix, apparently prolapsed into the cecum, was identified at celiotomy. An appendectomy with cecectomy was performed. On cut section, mucin was extruded from the lumen of the appendix. A mucinous neoplasm of the appendix with mucinous dissection to the serosal surface was reported at the time of frozen section. No gross ovarian pathology or peritoneal implants were noted. Cystadenoma with associated mucocele formation was verified by permanent histology. Mucocele of the vermiform appendix is a rare condition associated with neoplastic transformation in approximately 75% of all cases. Benign mucinous cystadenoma of the appendix should be differentiated from cystadenocarcinoma by frozen section at the time of celiotomy to ensure appropriate treatment. While systemic lupus erythematosus can lead to cutaneous mucinosis, an association with mucinous cystadenoma of the appendix has not been previously reported. Surveillance for metachronous colonic neoplasms is warranted in patients diagnosed with a mucinous neoplasm of the appendix.

Adult↗

PubMedDate not supplied

Preferential migration of CD62L cells into the appendix in mice with experimental chronic colitis.

BACKGROUND: Clinical and experimental studies suggest that appendectomy can protect against development of ulcerative colitis and Crohn's disease. However, how T cells in the appendix affect the development of colitis has not been clarified. AIM: To investigate the in vivo migration and activation of colitis-inducing CD62L+ cells during development of chronic colitis. METHODS: CD62L+CD4+ cells were fluorescently labeled and transferred to severe combined immunodeficient (SCID) mice to induce colitis. In vivo migration of T cells into the mucosa of the appendix and colon was quantified by in vivo microscopy after 7 weeks. In a second experiment, unlabeled CD62L+CD4+ cells were transferred, reisolated after 7 weeks, and adhesion molecule (integrin alpha4beta7) and costimulatory molecule (CD154) expression was analyzed. RESULTS: Six to eight weeks after CD62L+CD4+ cell transfer, SCID mice developed chronic colitis. In vivo microscopic analysis demonstrated a preferential migration of fluorescence-labeled CD62L+CD4+ cells into the mucosa of the appendix versus the colon. Re-isolation of lamina propria cells from mice with colitis confirmed that CD62L+CD4+ cell migration was significantly enhanced in the appendix, compared to the colon (3.5-fold). Furthermore, a higher proportion of CD62L+CD4+ cells re-isolated from the appendix expressed integrin alpha4beta7 and CD154 than from the colon. CONCLUSION: This study demonstrates the preferential migration of CD62L+CD4+ cells into the appendix as compared to the colon. This migration pattern correlated with upregulation of integrin alpha4beta7 and CD154 (CD40 ligand) on T cells. Our results suggest an important role of the appendix in the pathogenesis of colitis.

Adoptive Transfer↗

PubMed2002

[Variations in the position and point of origin of the vermiform appendix].

There were investigated variations of appendix vermiformis in the place of origin and position. The investigations were carried out on 50 human preparations of adults of both sexes, unintentional choice. The position and relation between intestinum caecum and appendix vermiformis were determined by forensic medical and pathoanatomical autopsy. Place of origin of appendix vermiformis, from wall of intestinum caecum is determined by anatomical dissection. Intestinum caecum has a variable shape and it occurs in two forms: conical, which dominates (56%) and square (44%). It has constant position in fossa iliaca dextra in 100% of 50 investigated cases. Appendix vermiformis is fully variable organ as for position and the place of origin from the wall of intestinum caecum. Dominantly (52%) it has rising position, and two subtypes are present: retrocecal (more expressed-38%) related to the retrocolic subtype (14%). Very frequent position of appendix vermiformis is a falling one (32%), in which pelvic position is more frequent (26%) related to descendent position (6%). Appendix vermifirmis is located subcaecaly in 8% of total number of investigated cases, found in three subtypes. It is found out that ostium appendicis vermiformis has a variable position in the wall of intestinum caecum. It is predominantly placed in the middle of the lower pole of the intestinum caecum (58%), in medial wall it is present in 32%, of all investigated, and in the lateral wall in the least number case 10%. The results of these investigations point out how important is to know variable anatomies of appendix vermiformis, for the clinical image of acute appendicitis is undoubtedly caused by the variable anatomical relations.

Appendix↗

PubMed1997

RAG1 and RAG2 in developing rabbit appendix subpopulations.

The appendix of young rabbits is a site of primary heavy chain variable region-gene diversification and B cell selection. Appendix cells from 6- to 9-wk-old rabbits were stained and sorted for surface CD43 and IgM. We found that the CD43+IgM- and double-negative CD43-IgM- cells contained RAG1 transcripts and RAG2 protein. The presence of RAG gene products in appendix raised the possibility that pro-/pre-B cells were present in young rabbit appendix. Although an early suggestion that RAG2 plays a role in variable region-gene diversification by gene conversion in chicken bursa was not supported by studies of RAG2 protein in this tissue, we produced anti-rabbit RAG2 Abs to determine whether RAG2 protein was present in rabbit appendix, where cells that recently underwent gene conversion are found. We detected RAG2 protein in the four subpopulations of rabbit appendix lymphocytes, distinguished by surface CD43 and IgM markers. The appearance of RAG gene products during different stages of B cell maturation may reflect the function of the young rabbit appendix as a site of both B cell development and diversification.

Amino Acid Sequence↗