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-mu+ delta-high 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 of memory B cells in T cell-dependent immune responses.