B cell antigen receptor specificity and surface density together determineB-1 versus B-2 cell development

Mice expressing the immunoglobulin (Ig) heavy (H) chain variable (V) region from a rearranged V(H)12 gene inserted into the IgH locus generate predomi nantly B-l cells, whereas expression of two other V-H region transgenes (V( H)B1-8 and V(H)glD42) leads to the almost exclusive generation of conventio nal, or B-2, cells. To determine the developmental potential of B cells bea ring two distinct B cell antigen receptors (BCRs), one favoring B-1 and the other favoring B-2 cell development, we crossed V(H)12 insertion mice with mice bearing either VHB 1-8 or V(H)glD42. B cells coexpressing V(H)12 and one of the other V-H genes are readily detected in the double IgH insertion mice, and are of the B-2 phenotype. In mice coexpressing VH12, V(H)B1-8 an d a transgenic kappa chain able to pair with both H chains, double H chain- expressing B-2 cells, and B-l cells that have lost V(H)B1-8 are generated, whereas V(H)B1-8 single producers are undetectable. These data suggest that B-1 but not B-2 cells are selected by antigenic stimuli in whose delivery BCR specificity and surface density are of critical importance.