Most peripheral B cells in mice are ligand selected

Using amplified cDNA and genomic libraries, we have analyzed the V_H gene repertoire of pre-B cells and various B cell subsets of conventional mice at the level of V_H genes belonging to the J558 V_H gene family. The sequence data were evaluated on the basis of a newly established list of 67 J558 V_H genes that comprise approximately two-thirds of the J558 V_H genes of the murine IgH^b haplotype. The results of the analysis demonstrate that V_H gene utilization in pre-B cells, although biased to some extent by B cell autonomous V_H gene selection, scatters over the whole range of J558 V_H genes present in the germline. In contrast, in mature, peripheral B cells comprising long-lived µ^+δhigh B cells as well as Ly-1 B cells, small overlapping sets of germline V_H genes are dominantly expressed. The data indicate that the recruitment of newly generated B cells into the long-lived peripheral B cell pool is mediated through positive selection by internal and/or external antigens. Because of the absence of immunoglobulin class switching and somatic hypermutation, this process is different from the selection ofmemory B cells in T cell-dependent immune responses.