Receptor tails unlock developmental checkpoints for B lymphocytes.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
P E Roth
Publications and source records attributed to P E Roth.
Assembly of the truncated immunoglobulin heavy chain D mu into antigen receptor-like complexes in pre-B cells but not in B cells.
Rearrangements of the IgH locus with JH joined to reading frame 2 of DH are greatly underrepresented in B cells. These rearrangements encode the truncated heavy chain D mu. In pre-B cells, we found D mu protein expressed on the cell surface and assembled into a complex with surrogate light chains, Ig alpha, and Ig beta. Cross-linking of either mu m- or D mu m- containing pre-B cell receptors triggered signal transduction reactions. In contrast, when expressed in mature B cell lines, D mu was not detected on the cell surface and did not efficiently bind kappa immunoglobulin light chains, but did associate with Ig alpha and Ig beta. These results characterize the interactions of D mu chain with other components of the B cell antigen receptor complex and suggest possible mechanisms by which D mu expression may interfere with B cell development.
Animals↗
Lymphocyte development. Intrinsic checkpoints for lineage progression.
A new T-cell receptor alpha-chain-like molecule has been identified in precursor T cells. This protein may be part of a receptor complex that induces T-cell maturation.
Animals↗
lambda 5, but not mu, is required for B cell maturation in a unique gamma 2b transgenic mouse line.
gamma 2b transgenic mice have a severe B cell defect, apparently caused by strong feedback inhibition of endogenous H-gene rearrangement coupled with an inability of gamma 2b to provide the survival/maturation functions of mu. A unique gamma 2b transgenic line, named the C line, was found to permit B cell development. When the C line is crossed with a mu-membrane knockout line, gamma 2b+ B cells develop in the homozygous knockout. In contrast, a transgenic line representative of all the other gamma 2b lines is completely B cell deficient when mu-mem is deleted. Strikingly, the C phenotype is dominant in C x other gamma 2b transgenic line crosses. There is no evidence for higher gamma 2b transgene expression or other position effects on the transgene in the C mouse. The sequences of the three gamma 2b transgene copies in the C line are identical to that of the original transgene. These results have led to the conclusion that in the C line the transgene integration constitutively induces a gene whose expression can replace mu. To more clearly delineate the stage at which the altered phenotype of the C line is expressed, C mice were crossed onto a lambda 5 knockout background. In the absence of lambda 5, the C line produces no B cells. Since it was also found that gamma 2b can associate with the surrogate light chain (sL; lambda 5/Vpre-B), the crosses between C line gamma 2b mice and lambda 5 knockout mice suggest that gamma 2b/sL is required for B cell maturation in this mouse line. Thus, gamma 2b alone is unable to replace mu for pre-B cell survival/maturation; however, in combination with an unknown factor and the sL, gamma 2b can provide these nurturing functions.
Alleles↗
Immunoglobulin gamma 2b transgenes inhibit heavy chain gene rearrangement, but cannot promote B cell development.
Transgenic mice with a gamma 2b transgene were produced to investigate whether gamma 2b can replace mu in the development of B lymphocytes. Transgenic gamma 2b is present on the surface of B cells. Young transgenic mice have a dramatic decrease in B cell numbers, however, older mice have almost normal B cell numbers. Strikingly, all gamma 2b-expressing B cells in the spleen also express mu. The same is true for mice with a hybrid transgene in which the mu transmembrane and intracytoplasmic sequences replace those of gamma 2b (gamma 2b-mumem). The B cell defect is not due to toxicity of gamma 2b since crosses between gamma 2b transgenic and mu transgenic mice have normal numbers of B cells. Presence of the gamma 2b transgene strongly enhances the feedback inhibition of endogenous heavy chain gene rearrangement. Light chain genes are expressed normally, and the early expression of transgenic light chains does not improve B cell maturation. When the endogenous mu locus is inactivated, B cells do not develop at all in gamma 2b transgenic mice. The data suggest that gamma 2b cannot replace mu in promoting the developmental maturation of B cells, but that it can cause feedback inhibition of heavy chain gene rearrangement. Thus, the signals for heavy chain feedback and B cell maturation appear to be different.
Animals↗
[Psoriasis: development and fatal complications].
In a retrospective study we tried to evaluate the number of severe psoriasis with a lethal outcome observed in France in a 20-year period from 1965 to 1985. Among 992 psoriatic in-patients on care during this period in the Dermatology Clinic of Strasbourg, 7 died of different complications directly related to the skin disease or its therapy; 39 further cases could be gathered through different departments of dermatology of France. Patients who died had generalized psoriasis (13 cases), psoriatic erythroderma (15 cases) and generalized pustular psoriasis (18 cases); 18 (39 p. 100) also had psoriatic polyarthritis. Circumstances leading to death (table I) were metabolic disorders, related to erythroderma in most cases, non-specific complications (infections, amyloidosis) or complications of specific treatments (methotrexate, etretinate, corticosteroids, mechlorethamine). A comprehensive review of the literature over a century showed that only 72 lethal psoriasis cases have been reported: this rather low number may be due to the fact that some rare pathologies, such as visceral amyloidosis (12 cases) (table III) and fatal complications of methotrexate therapy (38 cases) (table V), paradoxically are more often published than non-specific complications occurring in severe psoriasis, such as cardiovascular failure or cachexy in erythrodermic patients. However, the review of the literature shows, as our own inquiry, the poor prognosis of generalized pustular forms and of psoriasis-associated polyarthropathies: among 42 lethal cases where enough data were available, 23 (55 p. 100) had psoriatic polyarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗