T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice

Kei Ichi Nakayama, Keiko Nakayama, Lynn B. Dustin, Dennis Y. Loh

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Bcl-2 expression is tightly regulated during lymphocyte development. Mature lymphocytes in Bcl-2-deficient mice show accelerated spontaneous apoptosis in vivo and in vitro. Stimulation ofBcl-2-deficient lymphocytes by anti-CD3 antibody inhibited the spontaneous apoptosis not only in T cells but also in B cells. The rescue of B cells was dependent on the presence of T cells, mainly through CD40L and interleukin (IL)-4. Furthermore, we generated Bcl-2--deficient mice transgenic for a T cell receptor or an immunoglobulin, both specific for chicken ovalbumin, to test for antigen-specific T-B cell interaction in the inhibition of the spontaneous apoptosis. The initial T cell activation by antigenic peptides presented by B cells suppressed apoptosis in T cells. Subsequently, T cells expressed CD40L and released ILs, leading to the protection of B cells from spontaneous apoptosis. These results suggest that the antiapoptotic signaling via CD40 or IL-4 may be largely independent of Bcl-2. Engagement of the Ig alone was not sufficient for the inhibition of B cell apoptosis. Thus, the physiological role of Bcl-2 in mature lymphocytes may be to protect cells from spontaneous apoptosis and to extend their lifespans to increase the opportunity for T cells and B cells to interact with each other and specific antigens in secondary lymphoid tissues. Bcl-2, however, appears to be dispensable for survival once mature lymphocytes are activated by antigen-specific T-B cell collaboration.

Original languageEnglish
Pages (from-to)1101-1110
Number of pages10
JournalJournal of Experimental Medicine
Volume182
Issue number4
DOIs
Publication statusPublished - Oct 1 1995
Externally publishedYes

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Cell Communication
B-Lymphocytes
Lymphocytes
Apoptosis
T-Lymphocytes
CD40 Ligand
Viral Tumor Antigens
Interleukin-4
Ovalbumin
Lymphoid Tissue
T-Cell Antigen Receptor
Transgenic Mice
Immunoglobulins
Anti-Idiotypic Antibodies
Chickens
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice. / Nakayama, Kei Ichi; Nakayama, Keiko; Dustin, Lynn B.; Loh, Dennis Y.

In: Journal of Experimental Medicine, Vol. 182, No. 4, 01.10.1995, p. 1101-1110.

Research output: Contribution to journalArticle

Nakayama, Kei Ichi ; Nakayama, Keiko ; Dustin, Lynn B. ; Loh, Dennis Y. / T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice. In: Journal of Experimental Medicine. 1995 ; Vol. 182, No. 4. pp. 1101-1110.
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