The virgin B cell K:lambda ratio.
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Biomedical subjects
Publications and source records attributed to D A Ramsden.
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Immunoglobulin and T-cell receptor genes are somatically rearranged by site-specific recombination. Recombination signal sequences (RSS) have been identified as the major targeting element of this process. Recent reports demonstrate that differences in RSS affect the frequency of recombination, suggesting a role for RSS in the development of the B-cell repertoire. Examination of mouse light-chain RSS indicates that kappa light-chain RSS consistently show a greater degree of similarity to a consensus sequence than do those of lambda light chain. To determine whether this difference in natural RSS could affect the patterns of light-chain gene rearrangement and expression, we have constructed recombination substrates containing both a typical mouse kappa RSS pair and a typical mouse lambda RSS pair. Experiments using these substrates demonstrate that the kappa RSS pair mediates recombination at a vastly higher frequency than does the lambda RSS pair. This result argues that RSS differences may contribute significantly to the patterns of mouse immunoglobulin light-chain rearrangement, ultimately resulting in a high proportion of kappa light chain relative to lambda.
In this review, we have assembled some results on VH gene usage by mouse and human. We conclude that there is an early bias in usage of certain VH genes in both mouse and human. This biased usage has a strain dependent component as evidenced by its continued presence in the adult repertoire of some mouse strains, notably BALB/c, and not in others. The reason for the fetal bias is uncertain. However, the finding that the VH gene segments used in the human fetal repertoire are similar in sequence but not in chromosomal position to those expressed in the mouse fetal-repertoire leads us to suggest that the bias is not due to chromosomal location but rather may be reflecting the functioning of these gene products early in ontogeny.
Autoantibodies that bind aminoacyl-tRNA synthetases are strongly associated with the human inflammatory myopathies polymyositis and dermatomyositis, but their molecular origins and relationship to pathogenesis are not known. To address these issues, we wished to identify the autoantigenic epitopes which react with these autoantibodies and to this end, we previously isolated a full length cDNA clone encoding the target Ag recognized most frequently by myositis sera, histidyl-tRNA synthetase (HRS). In the present study, we have analyzed the HRS autoepitopes by two amino acid insertion linker mutagenesis of HRS proteins expressed in Cos 1 cells. A series of mutant HRS cDNA were constructed and the expressed proteins were tested for enzyme activity and for immune reactivity with a panel of sera with anti-Jo-1 antibodies. Immunoblotting and immunoprecipitation analyses revealed that anti-Jo-1 antibodies recognize multiple conformation-dependent and independent epitopes on HRS and that the autoepitopes vary among different myositis patients.
Records of 403 patients with gastric cancer seen between 1957 and 1966 at the Lahey Clinic Foundation have been analyzed. While the operability rate was 94 per cent and the resectability rate was 58 per cent, the cure rate was only 11 per cent and was unchanged from the previous decade. Significant correlation occurs with location, clinical type, histologic type, size of tumor, and number of lymph node metastases. The surgical approach is aggressive in exploration and in treating extensive but resectable cancers but is conservative for the average cancers and does not include resection of spleen, omentum, pancreas, and total stomach if possible. The histologic differentiation into diffuse and intestinal varieties provides additional prognostic information as well as clues to the etiology of varieties of gastric cancer.
Four cases of severe pseudomembranous colitis following the use of lincomycin and clindamycin are described; 2 required emergency total colectomy and 2 died. Cases of such gravity after the use of these drugs have not been previously reported. On hundred and fifty-six orthopaedic cases where clindamycin and lincomycin were used postoperatively are reviewed; 34 had diarrhoea (22 per cent), and 3 of the severe cases occurred in this group. The diagnosis of pseudomembranous colitis may be difficult as the latent period from initiation of drug therapy to commencement of diarrhoea may be as much as 18 days, and that from cessation of drug therapy may be as much as 11 days. The value of early sigmoidoscopy in cases of diarrhoea of obscure aetiology is emphasized, and the characteristic sigmoidoscopic and histological appearances of pseudomembranous colitis are described. As these drugs may produce a lethal condition it is suggested that they should be used with appropriate discretion, especially in the elderly female who appears to be most at risk.
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