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© The Rockefeller University Press, 0022-1007/1999/10/903/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 903-914

Selection at Multiple Checkpoints Focuses VH12 B Cell Differentiation toward a Single B-1 Cell Specificity

Calin Tatua, Jian Yea, Larry W. Arnolda, and Stephen H. Clarkea
a Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Correspondence to: Stephen H. Clarke, Dept. of Microbiology and Immunology, CB# 7290, 804 MEJB, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Tel:919-966-3131 Fax:919-962-8103 E-mail:shl{at}med.unc.edu.

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 VH12 and V{kappa}4/5H and are restricted in VHCDR3. We have previously reported that anti-PtC VHCDR3 is enriched among VH12-expressing cells by selective elimination of pre-B cells. We report here a bias for V{kappa}4/5H expression among VH12-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 VH12 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 V{kappa}4/5H-expressing cells. Thus, the bias for V{kappa}4/5H 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 VHCDR3 and L chain in a high frequency of VH12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.

Key Words: B-0 cells, B-1 cells, follicles, phosphatidyl choline, heavy and light chain association


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