Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and cytokine production by human B lymphocytes.
Class switching consists in the substitution of the heavy-chain constant region of immunoglobulin M (IgM) with that of IgG, IgA, or IgE. This enables antibodies to acquire new effector functions that are crucial to combat invading pathogens. Class switching usually requires engagement of CD40 on B cells by CD40 ligand (CD40L) on antigen-activated CD4(+) T cells and the production of cytokines. The process must be regulated tightly because abnormal IgG and IgA production favors the onset of autoimmunity, whereas increased switching to IgE leads to atopy. These inflammatory disorders can be triggered or exacerbated by costimulatory signals. Although thoroughly investigated on T cells, the roles of the inhibitory receptors CD85j, LAIR-1, and CD152 on B-cell functions have not been fully elucidated. In this study we show that cross-linking of the B-cell inhibitory receptors by specific monoclonal antibodies inhibits IgG and IgE production, reduces the percentage of IgG- and IgE-expressing B cells, and down-regulates interleukin 8 (IL-8), IL-10, and tumor necrosis factor alpha production. These effects were demonstrated using different B-cell stimulatory pathways (recall antigens, CD40L-transfected cells plus IL-4, and lipopolysaccharide plus IL-4). It thus appears that CD85j, LAIR-1, and CD152 play a central role for the control of IL-4-driven isotype switching.
Merlo
Andrea
A
Department of Experimental Medicine, Institute of Human Anatomy, University of Genova, Via De Toni 14, 16132 Genova, Italy.
Tenca
Claudya
C
Fais
Franco
F
Battini
Lorenzo
L
Ciccone
Ermanno
E
Grossi
Carlo E
CE
Saverino
Daniele
D
D000906:Antibodies; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D023201:CD40 Ligand / Q000494:pharmacology; D060908:CTLA-4 Antigen; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008070:Lipopolysaccharides / Q000494:pharmacology; D008211:Lymphocyte Cooperation; D011971:Receptors, Immunologic / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016209:Interleukin-8; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C108073:leukocyte-associated immunoglobulin-like receptor 1; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E