The functional roles of B cell membrane proteins belonging to the Fc receptor-like (FCRL) family are unclear. However, the demonstrated signaling capacities of FCRL suggest co-receptor functions that modulate B cell receptor (BCR) signaling. Nevertheless, the subsequent functional consequences of FCRL engagement are unknown. Using naive B cells obtained from peripheral blood of human subjects, we show that while FCRL5 surface protein is not present on resting cells, it is temporarily induced following BCR stimulation. Co-stimulation of FCRL5 and the BCR on B cells induced to express FCRL5 significantly enhanced proliferation in the presence of toll-like receptor 9 agonists. The same combination of stimuli led to the development of high proporsion of cells expressing the switched isotypes IgG and IgA on their surface. Optimal development of cells expressing downstream isotypes also required T cell help. Unexpectedly, IgG and IgA expression was most prominent on cells that underwent 1-3 cell divisions, suggesting an unusual mechanism. We suggest that FCRL5-dependent enhancement of proliferation and downstream isotype expression could play roles in the physiological expansion and development of antigen-primed B cells. Additionally, FCRL5 may contribute to tumor progression in hairy cell leukemia and other FCRL5 expressing B cell malignancies.
- Copyright © 2011 by The American Association of Immunologists, Inc.