Inappropriate expression of IgD from a transgene inhibits the function of antigen-specific memory B cells.
IgD expression has been shown to be downmodulated upon mitogenic or antigenic activation of B cells. To investigate whether this decrease is of functional significance we studied a mouse strain that expresses transgenic IgD on all B cells. The rearranged gene encoding the heavy chain of this IgD requires endogenous gene rearrangement before it can be expressed; therefore, normal B cell development is not affected. As a result, both transgenic IgD and endogenous IgM and IgD are expressed on all peripheral B cells. We show that the presence of extraneous IgD does not affect normal B cell activation by polyclonal stimulators, nor does it affect the primary IgM or IgG responses to TI or TD antigens. However, the secondary memory response is significantly diminished. The decrease is not attributable to a defective generation of memory B cells; instead the activation of memory cells appears to be compromised. Since the depressed response can be overcome by prior aggregation of the transgenic IgD with allotype-specific anti-IgD antibodies, it appears that persistence of the transgenic IgD on memory cells may influence their ability to be activated. Thus, the decrease in IgD expression on normal B cells after activation may be necessary for optimal activation of memory cells.
Yuan
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D
Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA. Yuan.Dorothy@pathology.swmed.edu
Dang
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T
Bibi
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R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007117:Immunization, Secondary; D007072:Immunoglobulin D / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000502:physiology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D019076:Transgenes; D014301:Trinitrobenzenes / Q000276:immunology
D006241:Haptens; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C020529:TNP-ficoll; D014301:Trinitrobenzenes; C033027:secretory IgM; C054401:trinitrophenyl keyhole limpet hemocyanin; D005362:Ficoll; D006433:Hemocyanins