Melatonin inhibits apoptosis during early B-cell development in mouse bonemarrow

The pineal secretory product, melatonin, exerts a variety of effects on the immune system. Administration of melatonin stimulates cell-mediated immuni ty, particularly by inhibiting apoptosis among T lymphocytes in the thymus and inducing production of T-cell-derived cytokines. However, its possible effects on the humoral immune system are unclear. In the present study, we have examined whether melatonin may influence the in vivo development of B lymphocytes in mouse bone marrow, a process in which apoptosis is normally a prominent feature. Double immunofluorescence labeling and flow cytometry were used to quantitate phenotypically defined precursor B-cell and mature B-cell populations and their apoptotic rates in bone marrow of mice fed eit her melatonin-containing or control diet for 16 days from 9 wk of age. In s hort-term bone marrow cultures, the incidence of apoptosis among large pre- B cells, including cells expressing the lambda 5 component of pre-B-cell re ceptor, was markedly reduced in melatonin-treated mice, associated with an increase in the absolute number of large pre-B cells in bone marrow. In con trast, apoptosis of earlier precursor B cells and mature B lymphocytes did not differ from control values. The results indicate that orally administer ed melatonin can substantially promote the survival of precursor B cells in mouse bone marrow. Melatonin treatment may thus boost the survival of newl y formed B cells mediating humoral immunity.