e n i c i d e M l a t n e m i r e p x E f o l a n r u o J e h T CORRESPONDENCE Raul M. Torres: torresr@njhealth.org Abbreviations used: dsRNA, double­ stranded RNA; MZ, marginal zone; PAMP, pathogen­ associated molecular pattern; PRR, pattern recognition receptor; TD, T cell dependent; TI, T cell independent; TLR, Toll­ like receptor. The Rockefeller University Press $30.00 J. Exp. Med. Vol. 207 No. 7 1485-1500 www.jem.org/cgi/doi/10.1084/jem.20092695 A r t i c l e Type I IFN enhances follicular B cell contr ibution to the T cell–independent antibody response Cristina L. Swanson,1 Timothy J. Wilson,2 Pamela Strauch,1 Marco Colonna,2 Roberta Pelanda,1 and Raul M. Torres1 1Integrated Department of Immunology, University of Colorado, Denver, and National Jewish Health, Denver, CO 80206 2Department of Pathology and Immunology, Washington University, St. Louis, MO 63110 Humoral immunity to viruses and encapsulated bacteria is comprised of T cell–independent type 2 (TI-2) antibody responses that are characterized by rapid antibody production by marginal zone and B1 B cells. We demonstrate that toll-like receptor (TLR) ligands influence the TI-2 antibody response not only by enhancing the overall magnitude but also by skewing this response to one that is dominated by IgG isotypes. Importantly, TLR ligands facilitate this response by inducing type I interferon (IFN), which in turn elicits rapid and significant amounts of antigen-specific IgG2c predominantly from FO (follicular) B cells. Furthermore, we show that although the IgG2c antibody response requires B cell– autonomous IFN- receptor signaling, it is independent of B cell–intrinsic TLR signaling. Thus, innate signals have the capacity to enhance TI-2 antibody responses by promoting participation of FO B cells, which then elaborate effective IgG anti-pathogen antibodies. The peripheral pool of mature B cells in adults is composed of several subpopulations, each of which is generally thought to make a distinct contribution to humoral immunity. As an ex­ ample, natural serum IgM functions as a first line of defense against pathogens and is pro­ duced primarily by B1a B cells before exposure (Baumgarth et al., 1999; Haas et al., 2005). Upon bacterial or viral infection, marginal zone (MZ) and B1 B cell subsets respond rapidly, constituting the immediate acquired antibody response (Martin et al., 2001). Finally, FO (fol­ licular) B cells dominate the delayed highly specific antibody response comprised by soma­ tically mutated higher affinity class­ switched antibodies and memory B cells. These latter processes occur in germinal center reactions that occur after productive interactions between responding B cells and antigen­ specific helper T cells (Martin and Kearney, 2002; McHeyzer­ Williams, 2003). The nature of the antigen itself can also dictate which B cell subset is recruited into an antibody response. Using model antigens in rodents, B cell antigens have been classified as either T cell independent (TI) or T cell depen­ dent (TD). TI antigens promote B cell prolifer­ ation, differentiation, and antibody production in the absence of T cells and are further clas­ sified into two subgroups: type I (TI­ 1) or type 2 (TI­ 2). TI­ 1 antigens are mitogens that stimulate all B cells to produce antibody in a polyclonal manner and irrespective of an­ tigen specificity. Physiological TI­ 1 antigens include Toll­ like receptor (TLR) ligands, such as LPS which is expressed by gram negative bacteria (Coutinho et al., 1974), or certain viral coat proteins (Berberian et al., 1993; Blutt et al., 2004). TI­ 2 antigens are instead com­ posed of repetitive epitopes displayed on a backbone that simultaneously engage multiple antigen receptors on the surface of antigen­ specific B cells. TI­ 2 antigens elicit robust IgM and IgG3 antibody production in a TI fashion, although the presence of noncognate T cell help promotes production of other IgG iso­ types (Mongini et al., 1984). These TI antigens include polysaccharides found on encapsulated bacteria and highly organized viral capsid pro­ teins such as those found on vesicular stomatitis virus and poliovirus (Bachmann et al., 1995; © 2010 Swanson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution– Noncommercial–Share Alike 3.0 Unported license, as described at http://creative- commons.org/licenses/by-nc-sa/3.0/). 1485