B Cell Antigen Receptor Specificity and Surface Density Together Determine B-1 versus B-2 Cell Development

Mice expressing the immunoglobulin (Ig) heavy (H) chain variable (V) region from a rearranged V_H12 gene inserted into the IgH locus generate predominantly B-1 cells, whereas expression of two other V_H region transgenes (V_HB1-8 and V_HglD42) leads to the almost exclusive generation of conventional, or B-2, cells. To determine the developmental potential of B cells bearing two distinct B cell antigen receptors (BCRs), one favoring B-1 and the other favoring B-2 cell development, we crossed V_H12 insertion mice with mice bearing either V_HB1-8 or V_HglD42. B cells coexpressing V_H12 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 V_H12, V_HB1-8 and a transgenic κ chain able to pair with both H chains, double H chain–expressing B-2 cells, and B-1 cells that have lost V_HB1-8 are generated, whereas V_HB1-8 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.