Abstract
The transmembrane glycoprotein CD83 is an important regulator of both thymic T cell maturation and peripheral T cell response. Recent studies suggested that CD83 is also involved in the regulation of B cell maturation, activation, and homeostasis. In this study, we show that in vivo overexpression of CD83 dose dependently interfered with the Ig response to thymus-dependent and thymus-independent model Ag immunization. CD83 deficiency, in contrast, which was restricted to B cells in mixed bone marrow chimeras, led to unchanged or even slightly increased Ig responses. Strikingly, the engagement of CD83 that is naturally up-regulated on wild-type B cells by injection of anti-CD83 mAb in vivo induced a 100-fold increase in the IgG1 response to immunization. Kinetic analysis revealed that CD83 had to be engaged simultaneously or shortly after the B cell activation through injection of Ag, to modulate the IgG1 secretion. Furthermore, using mixed bone marrow chimeras in which either selectively the B cells or the dendritic cells were CD83 deficient, we demonstrate that anti-CD83 mAb mediated its biologic effect by engaging CD83 on B cells and not on CD11c(+) dendritic cells. Taken together, we provide strong evidence that CD83 transduces regulatory signals into the very B cell on which it is expressed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation / genetics
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Antigens, CD / biosynthesis
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Antigens, CD / immunology*
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Antigens, CD / metabolism*
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism*
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CD83 Antigen
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Dose-Response Relationship, Immunologic
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Ficoll / administration & dosage
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Ficoll / immunology
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Haptens / administration & dosage
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Haptens / immunology
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Hemocyanins / administration & dosage
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Hemocyanins / immunology
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / blood
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Immunoglobulin M / biosynthesis
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Immunoglobulin M / blood
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Immunoglobulins / biosynthesis
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Immunoglobulins / deficiency
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Immunoglobulins / immunology*
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Immunoglobulins / metabolism*
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Immunosuppression Therapy
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Nitrophenols / administration & dosage
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Nitrophenols / immunology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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2,4-dinitrophenyl keyhole limpet hemocyanin
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Antigens, CD
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Haptens
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Immunoglobulin G
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Immunoglobulin M
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Immunoglobulins
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Membrane Glycoproteins
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Nitrophenols
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Ficoll
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Hemocyanins