Castration of normal male mice results in B cell expansion which is reversible with androgen replacement

Serum immunoglobulin levels are known to be higher in women. This sexual dimorphism is believed to be hormonally mediated, but the underlying cellular mechanisms are unknown. We report here that castration of normal adult male mice results in expansion of B cell populations in the spleen and bone marrow. Castration of either C57 BI/6 or DBA/2 mice was performed at 3 to 4 weeks of age and studies were carried out 3 weeks or more after surgery. In some experiments, animals were thymectomized at 3 weeks, castrated at 4 weeks and then studied 3 or more weeks later. Quantitation of cell populations was done using flow cytometry. Relative numbers of B220+ B cells in bone marrow were increased from 14% in intact C57 mice to 24% in castrates (p=0.009); a similar increase from 22% to 32% was observed in DBA/2 mice (p=0.003). Numbers of other bone marrow cells positive for either the monocyte/macrophage marker Mac-1 or for the erythroid precursor marker identified by the TER-119 antibody were not significantly changed in either strain (p≥0.10 for each). Androgen replacement in castrate mice given as 3 doses of either testosterone (1 mg) or dihydrotestosterone (0.2-0.4 mg) resulted in specific decreases in B220+ bone marrow cells to 65% of values measured in oil-treated castrate controls (p=0.03). Castration resulted in splenic enlargement (74 mg to 93 mg) with an increase in the proportion of B220 + cells from 43% to 58%; androgen replacement reversed this effect (p=0.05). Castration-induced splenic enlargement occurred in the presence or absence of the thymus. We conclude that androgens exert direct and reversible effects on the B cell compartment of the immune system.