Oestrogen receptor specificity in oestradiol-mediated effects on B lymphopoiesis and immunoglobulin production in male mice

Oestrogen treatment down-regulates B lymphopoiesis in the bone marrow of mice. Meanwhile it up-regulates immunoglobulin production. To understand better the oestrogen action on bone marrow male mice lacking oestrogen receptor alpha (ERalpha; ERKO mice), lacking ERbeta (BERKO mice), lacking both receptors (DERKO mice) or wild-type (wt) littermates were castrated and treated for 2.5 weeks with 30 mug/kg 17beta-oestradiol (E-2 ) or vehicle oil as controls. The B lymphopoiesis in the bone marrow was examined by flow cytometry and mature B-cell function was studied using an ELISPOT assay enumerating the B cells in bone marrow and spleen that were actively producing immunoglobulins. In wt mice the frequency of B-lymphopoietic (B220(+) ) cells in the bone marrow decreased from 15% to 5% upon E-2 treatment. In ERKO and BERKO mice significant reduction was seen but not of the same magnitude. In DERKO mice no reduction of B lymphopoiesis was seen. In addition, our results show that E-2 mediated reduction of different steps in B lymphopoiesis require only ERalpha or both receptors. In wt and BERKO mice E-2 treatment resulted in significantly increased levels of B cells actively producing immunoglobulin, while in ERKO and DERKO mice no such change was seen. Similar results were found in both bone marrow and spleen. In conclusion our results clearly show that both ERalpha and ERbeta are required for complete down-regulation of B lymphopoiesis while only ERalpha is needed to up-regulate immunoglobulin production in both bone marrow and spleen.