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T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death.

S Lederman, M J Yellin, A M Cleary, A Pernis, G Inghirami, L E Cohn, L R Covey, J J Lee, P Rothman and L Chess
J Immunol March 1, 1994, 152 (5) 2163-2171;
S Lederman
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M J Yellin
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A M Cleary
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A Pernis
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G Inghirami
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L E Cohn
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L R Covey
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J J Lee
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P Rothman
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L Chess
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Abstract

An important component of T cell help for B lymphocyte differentiation is the contact-dependent signaling mediated by the T cell-B cell activating molecule (T-BAM/CD40-L), an activation-induced surface membrane protein on CD4+ T helper cells in lymphoid follicles that interacts with the B cell surface molecule, CD40. The present study dissects the roles of T-BAM/CD40-L in helper function by means of a neutralizing anti-T-BAM/CD40-L mAb (5c8), a T-BAM/CD40-L-expressing T cell tumor subclone (Jurkat D1.1), and a T-BAM/CD40-L-responsive IgM+ B cell tumor of germinal center origin (RAMOS 266). Like activated T cells, D1.1 cells induce B cells to synthesize IgG, IgA, and IgE in a process that is specifically inhibited by the mAb 5c8. Although rIL-4 alone, but not Jurkat D1.1, induces IgH C gamma mRNA transcripts in RAMOS 266, the T-BAM/CD40-L molecule on D1.1 acts on rIL-4-primed RAMOS B cells to augment expression of C gamma transcripts. In addition, IgG+ RAMOS 266 clones were expanded from D1.1- and rIL-4-stimulated cultures that had undergone deletional IgH isotype switch recombination events. Furthermore, T-BAM/CD40-L signals delivered by the D1.1 clone dramatically rescue RAMOS 266 from mAb anti-IgM-induced apoptosis. Taken together, these data support the idea that T-BAM/CD40-L plays important roles in inducing Ig isotype switch recombination and the clonal selection of isotype-switched B cells.

  • Copyright © 1994 by American Association of Immunologists

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The Journal of Immunology
Vol. 152, Issue 5
1 Mar 1994
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T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death.
S Lederman, M J Yellin, A M Cleary, A Pernis, G Inghirami, L E Cohn, L R Covey, J J Lee, P Rothman, L Chess
The Journal of Immunology March 1, 1994, 152 (5) 2163-2171;

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T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death.
S Lederman, M J Yellin, A M Cleary, A Pernis, G Inghirami, L E Cohn, L R Covey, J J Lee, P Rothman, L Chess
The Journal of Immunology March 1, 1994, 152 (5) 2163-2171;
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Print ISSN 0022-1767        Online ISSN 1550-6606