SUPPRESSION OF B-LYMPHOPOIESIS DURING NORMAL-PREGNANCY

We describe a dramatic reduction in numbers and activity of committed B lymphocyte precursors in the bone marrow of normal pregnant mice. Ch anges in cells responsive to IL-7 were evident as early as 6.5 d of pr egnancy and values were <10% of normal at parturition. B lineage precu rsors, identified by display of CD45R and absence of surface IgM, were also substantially depressed, and subpopulations representing differe nt stages in the B lineage were assessed by three-color flow cytometry . Early pro-B cells are medium to large in size and have been previous ly characterized by low expression of the heat-stable antigen (HSA). T his category of cells was not reduced, and in fact may have been sligh tly elevated, during pregnancy. In contrast, all subsequent population s of B lineage precursors, defined by patterns of expression of heat-s table and CD43 antigens, were substantially depressed. The immediate p recursors of B cells (small pre-B cells) were identified by small size , expression of CD45R, absence of CD43, and lack of surface IgM. These were the most reduced of any phenotypically defined population in bon e marrow. Numbers of newly formed B cells, characterized by the presen ce of sIgM, but not sIgD, were also diminished. However, B cells with a mature phenotype (sIgM+, sIgD+) were present in normal to somewhat e levated numbers. Mitogen-responsive B cells clonable in a semisolid ag ar assay were not significantly affected. A bromodeoxyuridine (BrdU) l abeling technique was used to evaluate mitotic activity, which reveale d an increased proportion of long-lived lymphocytes in the bone marrow of pregnant mice. These observations indicate that B lymphopoiesis is markedly downregulated during pregnancy and that all precursor popula tions beyond the early pro-B cell stage are affected. The pregnancy-re lated changes in bone marrow were selective for B lineage precursors, as cells expressing myeloid and erythroid markers were not reduced. In spleen, evidence was obtained for partial depletion of one subset of B cells. These cells, which have been reported to be recent immigrants from marrow, are characterized as having high levels of sIgM and HSA. Changes in other major B lymphocyte subsets in the spleen were less r emarkable. When considered with results from the BrdU labeling procedu re, the findings indicate that both production and export of lymphocyt es from marrow may be substantially decreased. Numbers of B cell precu rsors were higher in postpartum animals whose litters were removed at birth, suggesting that lactation may prolong regeneration of lymphocyt e production. We also found that acute estrogen treatment selectively reduced numbers of B lymphocyte precursors in bone marrow. These obser vations raise the interesting possibility that endocrine mechanisms in volving sex steroids may be important for normal regulation of B lymph opoiesis.