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.
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.
Brinkmann
V
V
Ciba-Geigy Limited, Pharmaceuticals Research Division, Allergy/Immunology, Basel, Switzerland.
Heusser
C H
CH
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*
D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007073:Immunoglobulin E