title: T cell-dependent differentiation of human B cells into IgM, IgG, IgA, or IgE plasma cells: high rate of antibody production by IgE plasma cells, but limited clonal expansion of IgE precursors.
abstract: The development of human functional Ig precursors into plasma cells expressing IgM, IgG, IgA, or IgE was compared. Purified human B cells were stimulated at limiting dilution with irradiated EL4 helper cells, IL-2, and IL-4. B cells proliferated exponentially until Day 8 of culture. Nondividing plasma cells of all isotypes were detectable in ELISPOT assays between Days 8 and 10 and secreted 1.8 +/- 0.7 ng antibody per cell within 24 hr. This indicates that plasma cells of all isotypes, including IgE, bear a comparable potential to secrete antibody. It further shows that Ig switching does not delay the development into IgE plasma cells, despite that switching from IgM to IgE in vitro required 6 days of IL-4 action. The proliferation and Ig production by B cells readily declined after Days 8 and 10, respectively, and could not be prolonged by restimulating B cells with fresh helper cells and lymphokines in secondary cultures. This indicates that B cells have developed into nondividing, high rate Ig-secreting plasma cells within 9 days, and that they do not differentiate any further under the applied conditions. In contrast to IgM, IgG, and IgA committed B cells, IgE switched cells did not undergo clonal expansion, since the numbers of functional IgE precursors corresponded to the maximal numbers of IgE-secreting plasma cells, whereas the numbers of IgM-, IgG-, or IgA-secreting cells exceeded the number of functional precursors 15-fold. The results demonstrate that human B cells of all isotypes, including IgE, have the potential to secrete antibody at a comparably high rate, and that the IL-4-induced switch process does not delay the differentiation into plasma cells.
authors.affiliation: Ciba-Geigy Limited, Pharmaceuticals Research Division, Allergy/Immunology, Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Brinkmann
authors.forename: C H
authors.initials: CH
authors.lastname: Heusser
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D010950:Plasma Cells / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007073:Immunoglobulin E