The differentiation of human memory B cells into specific antibody-secreting cells is CD40 independent.
It is generally accepted that memory B cells can be defined by their ability to produce, upon antigenic challenge, somatically mutated antibody molecules characterized by an increased affinity and by the expression of a downstream heavy chain isotype. However, the inability to isolate this particular B cell compartment has precluded the study of memory B lymphocyte physiology in man. We previously reported on the identification of an IgD- B cell subset in human tonsils that we defined as CD38- B cells, whose phenotype is highly reminiscent of that of memory B lymphocytes from the splenic marginal zone of rodents. In the present study, we developed a model of the measles virus (MV)-specific secondary antibody response in vitro to assess the presence of memory B lymphocytes in different B cell subsets isolated from human tonsils and explore the activation requirements of human memory B cells. Our findings show that the memory B cell pool resides in the CD38- B cell subpopulation and that the differentiation of MV-activated memory B cells into antibody-secreting cells can be achieved upon co-stimulation with interleukin (IL)-2 and IL-10, but does not require engagement of CD40. Interestingly, the CD40-mediated signal was found to synergize with Ig-cross-linking agents for the proliferation of memory B cells, but strongly suppressed their capacity to differentiate along the plasmacytoid pathway. Collectively, our results suggest that the CD40 signaling pathway is instrumental for the clonal expansion of the memory B cell pool, but does not operate in the later phase of the response, which allows their maturation into antibody-secreting cells.
Silvy
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A
INSERM U 404, "Immunité et Vaccination" Institut Pasteur de Lyon, France.
Lagresle
C
C
Bella
C
C
Defrance
T
T
D000914:Antibodies, Viral / Q000096:biosynthesis; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008459:Measles virus / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
D000914:Antibodies, Viral; D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell