HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Autoantigen inhibits apoptosis of a human B cell leukemia that produces pathogenic rheumatoid factor.

Abstract
We studied a variant CD5- B cell chronic lymphocytic leukemia (CLL) cell population that produces pathologic IgM kappa rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell CLL, these leukemia cells rapidly undergo cell death hours after being placed in tissue culture. We find that addition of Ag (aggregated human IgG) enhances significantly the survival of these cells in vitro. Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the leukemia cells' surface IgM receptors with immobilized murine mAb specific for human Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack of bcl-2 expression may render these leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B cell leukemias and lymphomas.
AuthorsR Kobayashi, L Z Rassenti, G Meisenholder, D A Carson, T J Kipps
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 151 Issue 12 Pg. 7273-83 (Dec 15 1993) ISSN: 0022-1767 [Print] United States
PMID7505024 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, CD
  • Autoantigens
  • CD5 Antigens
  • Cytokines
  • DNA, Neoplasm
  • Immunoglobulin G
  • Rheumatoid Factor
Topics
  • Antigens, CD (metabolism)
  • Apoptosis (immunology)
  • Autoantigens
  • Base Sequence
  • CD5 Antigens
  • Cytokines (pharmacology)
  • DNA, Neoplasm (genetics, metabolism)
  • Gene Rearrangement, B-Lymphocyte
  • Genetic Variation
  • Humans
  • Immunoglobulin G (pharmacology)
  • In Vitro Techniques
  • Leukemia, B-Cell (genetics, immunology)
  • Molecular Sequence Data
  • Phenotype
  • Repetitive Sequences, Nucleic Acid
  • Rheumatoid Factor (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: