VH gene replacement in hyperselected B cells of the quasimonoclonal mouse.

The primary repertoire of the quasimonoclonal mouse is monospecific. However, among peripheral B cells, there is a high frequency of variant cells with V(H) replacements, which are also hypermutated. We show in this work that these hyperselected cells expand in numbers as the animals increase in age, switch their isotypes, and with increasing age become the almost exclusive contributors to the pool of serum Ig. The fraction of such cells is higher in the peritoneum than in peripheral blood, supporting the view that the peritoneum is a site of production of nonspecific serum Ig. We have also isolated and partially sequenced the replacing V(H) gene segments from B220-positive, Id-negative cells, and mu-negative, lambda-positive (i.e., switched) cells, and matched them with their germline counterparts. V(H) families are represented proportional to the number of members in the germline, a finding that is consistent with the idea that environmental Ag pressure maintains the germline repertoire of V gene segment.