HIV-gp160-induced T cell-dependent B cell differentiation: Role of T cell- B cell activation molecule and IL-6

N. Chirmule, V. S. Kalyanaraman, S. Lederman, N. Oyaizu, H. Yagura, M. J. Yellin, L. Chess, S. Pahwa

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The HIV envelope glycoprotein gp160 has been previously demonstrated to induce differentiation of normal B lymphocytes into Ig-secreting cells; the response is T cell-dependent, and T cells pretreated with gp160 can support B cell differentiation. This study investigates the cell surface molecules and cytokines that play a role in the gp160-induced T-B cell interaction. Utilizing CD4+CD45RO+ cloned T cells as the source of helper cells, we observed that physical contact with B cells is essential for the gp160-induced B cell response; no IgG-secretion occurred if T cells were separated from the B cells by culturing them in Transwell chambers. The expression of T cell-B cell activation molecule, a novel surface molecule associated with T cell activation, was moderately increased by gp160, and antibody to T cell-B cell activation molecule abrogated the gp160-mediated Th cell function. Cell surface molecules LFA-1, ICAM-1, HLA-DR, CD28, and B7 were also involved in the T-B cell interaction since mAb to any of these molecules inhibited the gp160-induced B cell differentiation response. gp160 also induced IL-6R and CD23 molecule expression on B cells when added to cultures of T plus B cells; there was CD23 expression only in cells that formed conjugates with T cells. Paraformaldehyde-fixed, gp160-pretreated T cells failed to elicit IgG responses in B cells, but did induce CD23 and IL-6R up-regulation on B cells. Addition of exogenous IL-6, but not IL-2 or IL-4, restored the IgG secretion. These findings indicate that the T cell dependence for gp160-induced B cell differentiation responses involves two steps: one requires contact-dependent interaction of several cell surface molecules, and the second requires IL-6 secretion.

Original languageEnglish (US)
Pages (from-to)2478-2486
Number of pages9
JournalJournal of Immunology
Volume150
Issue number6
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chirmule, N., Kalyanaraman, V. S., Lederman, S., Oyaizu, N., Yagura, H., Yellin, M. J., Chess, L., & Pahwa, S. (1993). HIV-gp160-induced T cell-dependent B cell differentiation: Role of T cell- B cell activation molecule and IL-6. Journal of Immunology, 150(6), 2478-2486.