DEVELOPMENT OF B-1 CELLS - SEGREGATION OF PHOSPHATIDYL CHOLINE-SPECIFIC B-CELLS TO THE B-1 POPULATION OCCURS AFTER IMMUNOGLOBULIN GENE-EXPRESSION

Adult mice have two easily recognizable subsets of B cells: the predominant resting population of the spleen, called B-2, and those called B-1, which predominate in coelomic cavities and can express CD5. Some antibody specificities appear to be unique to the B-1 population. Cells expressing antibody specific for phosphatidyl choline (PtC) are the most frequent, comprising 2-10% of peritoneal B cells in normal mice. To understand the basis for the segregation of the anti-PtC specificity to this population, we have produced transgenic (Tg) mice expressing the rearranged V(H)12 and V(K)4 genes of a PtC-specific B-1 cell lymphoma. We find that V(H)12-Tg and V(H)12/V(K)4 double-Tg mice develop very high numbers of PtC-specific peritoneal and splenic B cells. These cells have the characteristics of B-1 cells; most are CD5(+), and are all IgM(hi), B220(lo), and CD23(-). In the peritoneum these cells are also CD11b(+). In addition, adult mice have many splenic B cells (up to one third of Tg(+) cells) that express the V(H)12 Tg but do not bind PtC, presumably because they express a V-K gene other than V(K)4. These cells appear to be B-2 cells; they are CD23(+), CD11b(-), IgM(lo), B220(hi), and CD5(-), Thus, mice given either the V(H)12 Tg alone or together with the V(K)4 Tg develop a large population of PtC-specific B cells which belong exclusively to the B-1 population. Since B-2 cells can express the V(H)12 and V(K)4 gene separately, we interpret these data to indicate that the events leading to the segregation of PtC-specific B cells to the B-1 population in normal mice are initiated after Ig gene rearrangement and expression. These data are discussed with regard to hypotheses of the origin of B-1 cells. We also find that V(H)12-Tg mice have a marked decrease in the generation of Tg-expressing B cells in adult bone marrow, but not newborn liver. We speculate that this may be related to positive selection of V(H)12-expressing B cells during differentiation.