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* Department of Pathology and Laboratory Medicine,
Molecular Biology Institute, and
Microbiology and Molecular Genetics, University of California, Los Angeles, CA 90095;
Department of Medicine, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
¶ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110;
|| La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; and
# University of North Carolina, Chapel Hill, NC 27599
B cells are important in mucosal microbial homeostasis through their well-known role in secretory IgA production and their emerging role in mucosal immunoregulation. Several specialized intraintestinal B cell compartments have been characterized, but the nature of conventional B cells in the lamina propria is poorly understood. In this study, we identify a B cell population predominantly composed of surface IgM+ IgD+ cells residing in villi of the small intestine and superficial lamina propria of the large intestine, but distinct from the intraepithelial compartment or organized intestinal lymphoid structures. Small intestinal (villous) B cells are diminished in genotypes that alter the strength of BCR signaling (Bruton tyrosine kinasexid, G
i2–/–), and in mice lacking cognate BCR specificity. They are not dependent on enteric microbial sensing, because they are abundant in mice that are germfree or genetically deficient in TLR signaling. However, villous B cells are reduced in the absence of invariant NK T cells (J18–/– or CD1d–/– mice). These findings define a distinct population of conventional B cells in small intestinal villi, and suggest an immunologic link between CD1-restricted invariant NK T cells and this B cell population.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants DK46763 (to J.B. and M.K.), DK69434 (to J.B. and B.W.), AI058919 (to P.V.), GM07185 (to M.M.), DK34987 (to R.B.S.), RR018603 (to R.B.S.), and CA016042 (Jonsson Comprehensive Cancer Center Flow Cytometry); the Crohn’s and Colitis Foundation of America (to B.W. and R.D.N.); and the Broad Medical Research Foundation (to J.B.). The germfree animal facility at the Center for Gastrointestinal Biology and Disease at North Carolina State University was supported by a grant from National Institutes of Health (P30 DK349870).
2 Address correspondence and reprint requests to J. Braun, Pathology Center for Health Sciences 13–222, University of California-Los Angeles, Los Angeles, CA 90095-1732. E-mail address: jbraun{at}mednet.ucla.edu
3 Abbreviations used in this paper: LT, lymphotoxin; Btk, Bruton tyrosine kinase; ILF, isolated lymphoid follicle; IRF-3, IFN regulatory factor-3; LPL, lamina propria lymphocyte; PP, Peyer’s patch; SLP, superficial lamina propria; SPF, specific pathogen free; TRIF, Toll/IL-1 receptor domain-containing adaptor inducing IFN-β.
4 The online version of this article contains supplemental material.
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