title: LPS stimulates IgM production in vivo without help from non-B cells.
abstract: Gram-negative bacterial LPS induce murine B-cell activation and innate (polyclonal) Ab production. Mouse B cells express the LPS signaling receptor (TLR4), yet how LPS activates B-cell responses in vivo is not known. Can LPS directly stimulate B cells to induce innate Ab production? Is activation of non-B cells also required? To address these questions, we transfused LPS-responsive (Tlr4(+/+)) or non-responsive (Tlr4(-/-)) B cells into LPS-responsive or non-responsive mice. Increased expression of the early activation markers CD69 and CD86 could be induced on transfused Tlr4(-/-) B cells by injecting LPS subcutaneously into Tlr4(+/+) mice, demonstrating indirect activation of B cells by TLR4-responsive non-B cells in vivo, but the Tlr4(-) (/) (-) B cells did not increase serum IgM levels. In contrast, when Tlr4(-/-) recipients were transfused with Tlr4(+/+) B cells, LPS induced large amounts of serum IgM and LPS could also enhance specific Ab production to a protein that was co-injected with it (adjuvant response). Thus, LPS-exposed non-B cells mediated increased surface expression of early B-cell activation markers, but this response did not predict innate Ab responses or LPS adjuvanticity in vivo Direct stimulation of B cells by LPS via TLR4 was necessary and sufficient to induce B cells to produce Ab in vivo.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Research Center on Aging and Medicine, Fudan University, Shanghai, China Laboratory of Clinical Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA mingfanglu@fudan.edu.cn.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Lu
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Munford
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051940:B7-2 Antigen; D007075:Immunoglobulin M; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D000099192:CD69 Antigens; C493487:Tlr4 protein, mouse
keywords: B cells; Innate Ab; Lipopolysaccharide; Lymph node; Toll-like receptor 4