Rearrangement and selection of VH11 in the Ly-1 B cell lineage.
One of the predominant VH genes utilized to encode the anti-BrMRBC specificity is a member of the small VH11 family rearranged to JH1. Using the polymerase chain reaction (PCR) we have determined that the frequency of B cells with a VH11 rearrangement is 10-20 times higher in Ly-1 B than in Ly-1- "conventional" B cells regardless of location (spleen or peritoneal cavity). Conventional B cells rearrange this gene at comparable levels in pre-B cells and in mature B cells utilizing all JH gene segments. In contrast, the increased levels of VH11 rearrangement in Ly-1 B are restricted to JH1 (and some JH2) and therefore appear to be the result of selection. Furthermore, most peritoneal Ly-1 B cells with VH11 rearrangements fall in a fraction stained by anti-BrMRBC antibody, likely bearing multivalent natural (likely self) antigen constitutively bound to their surface Ig receptors. Thus, we suggest that autoantigens are largely responsible for the accumulation of autoantibody specificities in the Ly-1 B cell lineage with time, whereas they do not exert this effect in the conventional B cells.
Carmack
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Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Shinton
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SA
Hayakawa
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Hardy
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RR
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012641:Selection, Genetic
D000950:Antigens, Ly; D001323:Autoantibodies; D007135:Immunoglobulin Variable Region; D015345:Oligonucleotide Probes