In tonsils, CD138+ plasma cells (PCs) are surrounded by CD163+ resident macrophages (Mφs). We show here that human Mφs (isolated from tonsils or generated from monocytes in vitro) drive activated B cells to differentiate into CD138+CD38++ PCs through secreted CXCL10/IP-10 and VCAM-1 contact. IP-10 production by Mφs is induced by B cell-derived IL-6 and depends on STAT3 phosphorylation. Furthermore, IP-10 amplifies the production of IL-6 by B cells, which sustains the STAT3 signals that lead to PC differentiation. IP-10- deficient mice challenged with NP-Ficoll show a decreased frequency of NP-specific PCs and lower titers of antibodies. Thus, our results reveal a novel dialog between Mφs and B cells, in which IP-10 acts as a PC differentiation factor.
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