Document Detail

Rescue from anti-IgM-induced programmed cell death by the B cell surface proteins CD20 and CD40.
MedLine Citation:
PMID:  1280225     Owner:  NLM     Status:  MEDLINE    
Programmed cell death (PCD), or apoptosis, is characterized by several morphologic alterations and eventual cleavage of nuclear DNA into oligonucleo-some-length fragments. We defined a human B cell line, Ramos, that responds with PCD following ligation of surface IgM. Of the DNA in Ramos cells 3%-10% was fragmented as early as 4 h after IgM ligation. Propidium iodide staining demonstrated that 20%-40% of Ramos cells became apoptotic by 18 h and further established that cells transiting into the S phase of the cell cycle were susceptible to PCD. Addition of several agents to the Ramos cells abrogated anti-IgM-induced PCD, including the phorbol 12-myristate 13-acetate (PMA). In contrast to the effect of PMA, the 4 alpha PMA isomer of PMA neither activated protein kinase C (PKC) nor rescued the cells from anti-IgM-induced PCD, confirming a role for PKC in negating apoptosis. To explore the effect of physiologic signals on anti-IgM-induced PCD, antibodies against the CD20 or CD40 molecules were added in concert with anti-IgM. Both CD20 and CD40 synergize with anti-IgM to augment proliferation but neither molecule activates PKC in Ramos cells. Both anti-CD20 and anti-CD40 reduced the number of cells undergoing anti-IgM-induced PCD. Unlike the effect of anti-CD40, addition of anti-CD20 to anti-IgM-stimulated cells negated PCD only in a subset of cells. Maximal rescue occurred following the addition of anti-CD40 and occurred by 4 h and at least up to 20 h of culture. These data show that (a) PCD can be initiated in B cells entering the S phase of the cell cycle, (b) PCD can be triggered by engagement of surface IgM in the absence of ancillary signals or PKC activation, and (c) rescue from PCD can occur by several mechanisms, either PKC dependent or PKC independent.
M A Valentine; K A Licciardi
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of immunology     Volume:  22     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  1992 Dec 
Date Detail:
Created Date:  1992-12-29     Completed Date:  1992-12-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  3141-8     Citation Subset:  IM    
Department of Microbiology, University of Washington, Seattle 98195.
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MeSH Terms
Antigens, CD / physiology*
Antigens, CD20
Antigens, CD40
Antigens, Differentiation, B-Lymphocyte / physiology*
B-Lymphocytes / immunology*
Cell Line
DNA / metabolism
G1 Phase
Immunoglobulin M / immunology*
Protein Kinase C / physiology
S Phase
Tetradecanoylphorbol Acetate / pharmacology
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD20; 0/Antigens, CD40; 0/Antigens, Differentiation, B-Lymphocyte; 0/Immunoglobulin M; 16561-29-8/Tetradecanoylphorbol Acetate; 9007-49-2/DNA; EC Kinase C

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