Identification of centerin: A novel human germinal center B cell-restricted serpin Academic Article Article uri icon

Overview

MeSH Major

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation
  • Interleukins
  • T-Lymphocytes, Regulatory

abstract

  • For naive B cells to mature in response to antigen triggering and become either plasma cells or memory B cells, a complex array of events takes place within germinal centers (GC) of secondary lymphoid organs. With the long-term objective of defining and characterizing molecules that control the generation of GC, we have subtracted RNA messages derived from highly purified B cells at the follicular mantle stage of differentiation from GC B cells. Using this approach, we have identified a novel molecule, centerin, belonging to the family of serine-protease inhibitors or serpins. Transcription of centerin is highly restricted to GC B cells and their malignant counterparts, Burkitt's lymphoma lines. The putative centerin protein shares the highest sequence identity with thyroxine-binding globulin and possesses arginine/serine at its P1/P1' active site, suggesting that it interacts with a trypsin-like protease(s). In addition, several other sequence features of centerin also indicate that it serves as a bonafide protease inhibitor. Finally, we demonstrate differentially up-regulated transcription of this novel gene by resting, naive B cells stimulated in vitro via CD40 signaling, while Staphylococcus aureus Cowan strain-mediated B cell activation fails to generate this reponse. Because CD40 signaling is required for naive B cells to enter the GC reaction and for GC B cells to survive, it is likely that centerin plays a role in the development and/or sustaining of GC.

publication date

  • November 2000

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1002/1521-4141(200010)30:10<3039::AID-IMMU3039>3.0.CO;2-H

PubMed ID

  • 11069088

Additional Document Info

start page

  • 3039

end page

  • 48

volume

  • 30

number

  • 10