Generation of nondividing high rate Ig-secreting plasma cells in cultures of human B cells stimulated with anti-CD3-activated T cells

J Immunol. 1992 Jan 15;148(2):404-10.

Abstract

The capacity of human B cells to differentiate into high rate nondividing antibody-secreting plasma cells was investigated. Highly purified human peripheral blood B cells were stimulated with polyclonal B cell activators in the presence of a variety of recombinant cytokines (IL-2, IL-4, IL-6). Maximal production of Ig of all isotypes was observed when B cells were stimulated with intact T cells that were activated with mAb to the CD3 molecular complex. In these cultures, Ig production continued for more than 16 days. Moreover, differentiation to nondividing high rate Ig-producing cells was induced, as evidenced by a ninefold increase in the amount of Ig produced per Ig-secreting cell and the acquisition of resistance of ongoing Ig secretion to the inhibitor of DNA synthesis, hydroxyurea. To determine whether intact T cells were required for the entire culture period to achieve maximal Ig production, B cells were cultured with activated T cells for various lengths of time, reisolated and cultured with fresh activated T cells or various cytokines, then analyzed for Ig secretion. B cells preactivated for 6 days with anti-CD3-stimulated T cells required contact with intact T cells for continued Ig secretion. However, after 9 days of preactivation, dividing B cells responded maximally to anti-CD3-stimulated T cells, whereas cytokines were able to drive continued IgG secretion by nondividing B cells in the absence of intact T cells. IL-6 alone, or in combination with either IL-2 or IL-4, was the major cytokine driving ongoing Ig secreting by nondividing preactivated B cells. These results suggest that continued clonal expansion of Ig-secreting B cell blasts requires intact anti-CD3-activated T cells, whereas terminal differentiation of B cells into plasma cells after extensive clonal expansion is driven by cytokines, most notably IL-6.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibody-Producing Cells / physiology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • B-Lymphocytes / immunology*
  • CD3 Complex
  • Cells, Cultured
  • Humans
  • Immunoglobulins / biosynthesis*
  • Interleukin-2 / pharmacology
  • Interleukin-6 / pharmacology
  • Lymphocyte Activation*
  • Plasma Cells / physiology*
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / physiology*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Immunoglobulins
  • Interleukin-2
  • Interleukin-6
  • Receptors, Antigen, T-Cell