Human memory B cells isolated from blood and tonsils are functionally distinctive

Human B-cell studies in vitro have routinely used B lymphocytes purified from spleen, blood or tonsils irrespective of potential differences in their immunological traits. In this study, we compared the functional responses of total (CD19(+)) and memory B cells (B-mem; CD19(+)/CD27(+)) isolated from blood and tonsils to different stimuli. Peripheral B cells showed enhanced survival and proliferation compared with their tonsillar equivalents when stimulated for 10 days. Stimulated B cells from both tissues secreted significantly greater amounts of cytokines than unstimulated controls demonstrating their functional responsiveness. Analysis of CD27 expression over time indicated that the conditions that promoted survival and proliferation of peripheral Bmem, caused massive tonsillar B-mem death. Purified tonsillar B-mem failed to expand but rapidly differentiated in antibody secreting cells and subsequently underwent apoptosis. In contrast, circulating B-mem showed delayed activation and differentiation, but exhibited a longer lifespan and active proliferation. In addition, short-term stimulation of tonsillar B-mem resulted in the production of more immunoglobulin G (IgG) than their peripheral counterparts. At later time points, however, IgG production from the different B cells was reversed. Our findings imply that the tissue located and peripheral B-mem have distinct behaviors, indicating organ dependent functional responses that should not be generalizable to all B-mem. This work provides a greater understanding of how B-mem location is coupled to specialized roles of B lymphocytes.