Lymphokine-induction of memory B-cell differentiation: differential stimulation of large virgin and memory B-cell differentiation.
In order to compare and contrast the requirements of virgin and memory B cells for B-cell differentiation factors, a model system was developed in which low-density rat B cells isolated from 4-week primed antigen-draining lymph nodes were cultured in vitro. This large low-density cell population contained B cells which were 90% surface IgM positive and 60% IgD positive and showed moderately elevated Ia staining. When the cell population was stimulated with antigen plus lymphokines or lymphokines alone, antigen-specific IgG antibody was secreted; this was used as a measure of memory cell differentiation. When the cell population was stimulated with mitogen (lipopolysaccharide plus dextran sulfate) plus lymphokines, polyclonal IgG and IgM secretion was seen and was used as a measure of virgin B-cell differentiation. Using this system, we found that lymphokines contained in a Con A-induced rat spleen cell supernatant (CSN) were sufficient to drive both memory and virgin B-cell differentiation. In contrast, lymphokines contained in the supernatant from the murine T-cell hybridoma B151K12 (B151CFS) were able to induce large amounts of polyclonal IgM and IgG secretion but did not support memory B-cell differentiation. When recombinant human IL-2 was added to these cultures, it acted synergistically to augment virgin B-cell differentiation, but this combination of lymphokines was still not able to support memory B-cell differentiation. Furthermore, recombinant rat interferon-gamma and a commercial source of human BCGF, with or without IL-2, were unable to promote significant virgin or memory B-cell differentiation. These data support the hypothesis that memory B cells and virgin B cells differ in their lymphokine requirements for differentiation into antibody-secreting cells.
Leitenberg
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Department of Microbiology, University of Iowa, Iowa City.
Burg
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Feldbush
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D000818:Animals; D000941:Antigens; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D007074:Immunoglobulin G; D008222:Lymphokines