Macrophages induce differentiation of plasma cells through CXCL10/IP-10

In tonsils, CD138(+) plasma cells (PCs) are surrounded by CD163(+) resident macrophages (M phi s). We show here that human M phi s (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 M phi s 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 M phi s and B cells, in which IP-10 acts as a PC differentiation factor.