The CD19 signal transduction molecule is a response regulator of B-lymphocyte differentiation.
The phenotypes of CD19-deficient (CD19-/-) mice, and human CD19-transgenic (hCD19TG) mice that overexpress CD19 indicate that CD19 is a response regulator of B-lymphocyte surface receptor signaling. To further characterize the function of CD19 during B-cell differentiation, humoral immune responses to a T-cell-independent type 1 [trinitrophenyl-lipopolysaccharide (TNP-LPS)], a T-cell-independent type 2 [dinitrophenyl (DNP)-Ficoll], and a T-cell-dependent [DNP-keyhole limpet hemocyanin (KLH)] antigen were assessed in CD19-/- and hCD19TG mice. B cells from CD19-/- mice differentiated and underwent immunoglobulin isotype switching in vitro in response to mitogens and cytokines. In vivo, CD19-/- mice generated humoral responses to TNP-LPS and DNP-KLH that were dramatically lower than those of wild-type littermates. Surprisingly, the humoral response to DNP-Ficoll was significantly greater in CD19-/- mice. In contrast, hCD19TG mice were hyperresponsive to TNP-LPS and DNP-KLH immunization but were hyporesponsive to DNP-Ficoll. These results demonstrate that CD19 is not required for B-cell differentiation and isotype switching but serves as a response regulator which modulates B-cell differentiation. Since humoral responses to both T-cell-dependent and T-cell-independent antigens were similarly affected by alterations in CD19 expression, these differences are most likely to result from intrinsic changes in B-cell function rather than from the selective disruption of B-cell interactions with T cells.
Sato
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Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Steeber
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Tedder
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D000818:Animals; D000917:Antibody Formation; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology
C042158:2,4-dinitrophenyl keyhole limpet hemocyanin; D018941:Antigens, CD19; D007136:Immunoglobulins; D008070:Lipopolysaccharides; C048761:trinitrophenyl-lipopolysaccharide; D006433:Hemocyanins