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Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE John H. Kehrl: jkehrl{at}niaid.nih.gov

B lymphocyte–intrinsic Toll-like receptor (TLR) signals amplify humoral immunity and can exacerbate autoimmune diseases. We identify a new mechanism by which TLR signals may contribute to autoimmunity and chronic inflammation. We show that TLR4 signaling enhances B lymphocyte trafficking into lymph nodes (LNs), induces B lymphocyte clustering and interactions within LN follicles, leads to sustained in vivo B cell proliferation, overcomes the restriction that limits the access of nonantigen-activated B cells to germinal center dark zones, and enhances the generation of memory and plasma cells. Intravital microscopy and in vivo tracking studies of B cells transferred to recipient mice revealed that TLR4-activated, but not nonstimulated, B cells accumulated within the dark zones of preexisting germinal centers even when transferred with antigen-specific B cells. The TLR4-activated cells persist much better than nonstimulated cells, expanding both within the memory and plasma cell compartments. TLR-mediated activation of B cells may help to feed and stabilize the spontaneous and ectopic germinal centers that are so commonly found in autoimmune individuals and that accompany chronic inflammation.

Abbreviations used: BAFF, B cell–activating factor of the tumor necrosis factor family; BCR, B cell antigen receptor; FDC, follicular DC; HEL, hen egg lysozyme; iLN, inguinal LN; MIP, maximum intensity projection; PLN, popliteal LN; TLR, toll-like receptor; TP-LSM, two-photon laser-scanning microscopy; TRIF, TIR domain–containing adapter-inducing IFN-β.

© 2009 The Rockefeller University Press
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