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

Abstract

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 (Bmem; 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 Bmem death. Purified tonsillar Bmem failed to expand but rapidly differentiated in antibody secreting cells and subsequently underwent apoptosis. In contrast, circulating Bmem showed delayed activation and differentiation, but exhibited a longer lifespan and active proliferation. In addition, short-term stimulation of tonsillar Bmem 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 Bmem have distinct behaviors, indicating organ dependent functional responses that should not be generalizable to all Bmem. This work provides a greater understanding of how Bmem location is coupled to specialized roles of B lymphocytes.

Extinct type of human parvovirus B19 persists in tonsillar B cells

“…This may reflect the rapid turnover of circulating B cells (from a few days to 5–6 weeks)23 and/or their difference in phenotype as compared to tonsillar B cells2425.…”

Changes in Tonsil B Cell Phenotypes and EBV Receptor Expression in Children Under 5‐Years‐Old

“…Since then, the proportions of different B cell subsets in human palatine tonsils have been documented for adults, adolescents, and older children (25), but to our knowledge no study has measured the changes in B cell subsets of human tonsils in early childhood (< 4 years of age). And despite interest in the cell types and function of tonsil B cells (26)(27)(28), studies have not focused on children under 5 years of age. This age range is critical for understanding the unique immune interface of the palatine tonsils when they are most highly developed (4) and during the ages when palatine tonsils play their most important physiological role in defense against oral pathogens.…”

Donors define whether CD19+CD27+ tonsillar B cells are mostly memory or germinal‐center B cells

“…CD27 has been used by numerous independent groups as a pan‐memory B‐cell marker not only for the identification of peripheral blood (PB) memory B cells (B mem ) but also for spleen B mem , 1 , 2 tonsillar B mem 3 and bone marrow B mem 4 . Through a Letter to the Editor, Kupperś group has criticized the experimental approach we used (that is, using only CD27 as a human‐B mem marker in tonsils) in the article in which we report a comparative analysis of human B mem derived from PB and tonsils 5 . We would like, in turn, to respond and address the issue.…”

“…Even if contaminating levels were not as high as those alleged in the Letter to the Editor, we acknowledged that the sorting strategy used left around a 20% putative GC B cells in our B mem sample that we disregarded. We did it on the basis of previous findings 6 that showed that 75% of such GC B cells are dead within 16 h of culture, which means that it would be unlikely that they would have any influence on the culture behavior observed at days 2, 5 and 6 (reported in Figure 2 in Perez et al 5 ). Generation of antibody‐secreting cells (ASC), cell proliferation and Ig production at those time points are likely to result from the dominating fraction of tonsillar B mem in culture, being indeed usual functional responses of such a population of cells.…”