Regulation of frontline antibody responses by innate immune signals
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IMMUNOLOGY AT MOUNT SINAI
Regulation of frontline antibody responses by innate immune signals Alejo Chorny • Irene Puga • Andrea Cerutti
Andrea Cerutti Ó Springer Science+Business Media, LLC 2012
Abstract Mature B cells generate protective immunity by undergoing immunoglobulin (Ig) class switching and somatic hypermutation, two Ig gene-diversifying processes that usually require cognate interactions with T cells that express CD40 ligand. This T-cell-dependent pathway provides immunological memory but is relatively slow to occur. Thus, it must be integrated with a faster, T-cell-independent pathway for B-cell activation through CD40 ligand-like molecules that are released by innate immune cells in response to microbial products. Here, we discuss recent advances in our understanding of the interplay between the innate immune system and B cells, particularly ‘‘frontline’’ B cells located in the marginal zone of the spleen and in the intestine. Keywords
B cells Innate immune cells Splenic marginal zone Intestinal mucosa Class switching
Introduction The mammalian immune system is composed of innate and adaptive branches that mount integrated responses to combat invading pathogens while preserving homeostasis at mucosal sites colonized by commensal bacteria [1]. Dendritic cells (DCs), monocytes, macrophages, granulocytes, natural killer cells, and epithelial cells of the innate immune system mediate fast but nonspecific protective responses after recognizing generic microbial structures
A. Chorny A. Cerutti Department of Medicine, The Immunology Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA A. Chorny I. Puga A. Cerutti (&) Municipal Institute for Medical Research (IMIM)-Hospital del Mar, Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88 Avenue, 08003 Barcelona, Spain e-mail: [email protected]; [email protected] A. Cerutti Catalan Institute for Research and Advanced Studies (ICREA), Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88 Avenue, 08003 Barcelona, Spain
through germ line gene-encoded receptors often referred to as pattern recognition receptors (PRRs), which include Toll-like receptor (TLR) family members [2, 3]. In contrast, T and B cells of the adaptive immune system mediate specific but temporally delayed responses after recognizing discrete antigenic epitopes through somatically recombined receptors. After sensing microbial signatures through PRRs, innate immune cells such as DCs undergo maturation and acquire the ability to present antigenic peptides to T cells, thereby initiating highly specific cellular and humoral responses [4–6]. The latter involve production of highly diversified antibody molecules that include immunoglobulin M (IgM), IgG, IgA, and IgE. In addition to receiving stimulating signals from antigen-activated T cells, B cells can initiate Ig production after responding to activating signals from cells of the innate immune system. Unlike T-cell-dependent (TD) antibody responses, which predominantly involve fol
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