Germinal center B cells rescued from apoptosis by CD40 ligation or attachment to follicular dendritic cells, but not by engagement of surface immunoglobulin or adhesion receptors, become resistant to CD95‐induced apoptosis
作者:
Gerrit Koopman,
Robert M. J. Keehnen,
Ernst Lindhout,
David F. H. Zhou,
Cornelis De Groot,
Steven T. Pals,
期刊:
European Journal of Immunology
(WILEY Available online 1997)
卷期:
Volume 27,
issue 1
页码: 1-7
ISSN:0014-2980
年代: 1997
DOI:10.1002/eji.1830270102
出版商: WILEY‐VCH Verlag GmbH
关键词: Germinal center;Apoptosis;CD40
数据来源: WILEY
摘要:
AbstractGerminal centers (GC) constitute a specialized microenvironment essential for the formation of memory B cells, B cell affinity maturation and isotype switching. Within the GC, the B cells closely interact with follicular dendritic cells (FDC) and T cells, which both provide stimuli to the B cells that prevent their entry into apoptosis and promote their differentiation into memory cells or plasma cells. Cross‐linking of B cell immunoglobulin (Ig) receptors by antigen, stimulation of the integrin adhesion molecules LFA‐1 and VLA‐4 on the B cell through interaction with their counter receptors ICAM‐1 and VCAM‐1 on the FDC and cross‐linking of CD40 on the B cells through interaction with the CD40 ligand (CD40L) on T cells have been shown to prevent entry into apoptosis of GC B cells. Triggering of CD95, on the other hand, has been shown to induce apoptosis. We therefore investigated the interaction between adhesion‐mediated signals, Ig, CD40, and CD95. The spontaneous apoptosis of GC B cells was not further increased by adding anti‐CD95. However. CD95 stimulation did result in apoptosis of GC B cells in the presence of anti‐Ig or adhesion‐mediated rescue signals, which indicates that CD95 expressed on GC B cells is functionally active. In contrast, anti‐CD95 was unable to induce apoptosis in cells rescued via CD40 stimulation, suggesting an important role for CD40L expressed on GC T cells in apoptosis regulation. We also studied apoptosis of B cells adhering to FDC, and found that B cells that interact with FDC were also rescued from CD95‐induced apoptosis. A human CD40.Fcu fusion protein that blocks CD40 ligation failed to inhibit this effect. Our studies therefore indicate that neither CD40, Ig receptors, nor adhesion receptors mediate rescu
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