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Publication : Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity.

First Author  Tatu C Year  1999
Journal  J Exp Med Volume  190
Issue  7 Pages  903-14
PubMed ID  10510080 Mgi Jnum  J:115090
Mgi Id  MGI:3690660 Doi  10.1084/jem.190.7.903
Citation  Tatu C, et al. (1999) Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity. J Exp Med 190(7):903-14
abstractText  Phosphatidyl choline (PtC)-specific B cells segregate to the B-1 subset, where they comprise up to 10% of the B-1 repertoire. About half express V(H)12 and Vkappa4/5H and are restricted in V(H)CDR3. We have previously reported that anti-PtC V(H)CDR3 is enriched among V(H)12-expressing cells by selective elimination of pre-B cells. We report here a bias for Vkappa4/5H expression among V(H)12-expressing B cells, even among those that do not bind PtC and are not B-1. This is due in part to an inability of V(H)12 to associate with many light (L) chains but must also be due to a selective advantage in survival or clonal expansion in the periphery for Vkappa4/5H-expressing cells. Thus, the bias for Vkappa4/5H expression is independent of PtC binding, and, as segregation to B-1 occurs after Ig gene expression, it precedes segregation to the B-1 subset. In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells. These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.
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