Human memory B cells exhibit different functional responses depending on their tissue localization

PÉREZ, MA EUGENIA; BILLORDO, ARIEL; VILLALBA, MA INÉS; FAINBOIM, LEONARDO; ARANA, ELOÍSA

Lima

Congreso; Reunión de la Asociación Latinoamericana de Inmunología; 2012

Asociación Latinoamericana de Inmunología

Activated B cells in secondary lymphoid organs (SLO) can differentiate along two distinct pathways. On the one hand, B cells can differentiate to form extrafollicular plasmablasts that are essential for rapid antibody production. On the other hand, activated B cells can enter germinal centres, where they can differentiate into plasma cells (which can secrete high-affinity antibody) or memory B cells (which confer long-lasting protection from secondary challenge with antigen). Memory B cells return to peripheral blood and recirculate throughout the body and between SLOs. In this study, we have compared functional responses of B cells isolated from peripheral blood (PB) with those isolated from human tonsils (SLO). Initially, we investigated their proliferative capacity in cultures supplemented with IL-2+IL-4+CD40L+αIgs. Following 10 days of culture, B cells isolated from PB, presented 5 generations of healthy daughter cells while tonsillar B cells showed none, with a mortality of 80%. Furthermore, PB B lymphocytes secreted 400% more IL-6 than tonsillar B cells, in response either to T-cell derived stimulus or to a T-independent one. Also, IL-8 levels from SLO B cells resulted between 10 or 5 times lower, depending on the stimulus, compared with PB B lymphocytes. Such differences are not attributable merely to the distinct initial proportion of memory B cells (CD20+CD27+) on both tissues. When we analyzed CD27 expression post culture, we found that the percentage of memory B cells increases steadily with B cells isolated from PB. Notably, it decreases significantly on tonsillar B cell cultures. We observed this behavior with all stimuli assayed. Finally, we sorted CD20+CD27+ cells from PB and tonsils. Peripheral memory B lymphocytes showed slower kinetic of activation and higher viability and proliferation rate than their tonsillar counterparts. Also, they secreted significantly higher level of IgM when stimulated, in relation to SLO memory B cells. Taken together, these results show that there are functionally distinct memory B cell subsets located differentially in PB and SLOs.