Identification of centerin: a novel human germinal center B cell-restricted serpin.

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.

• Authors: J K Frazer, D G Jackson, J P Gaillard, M Lutter, Y J Liu, J Banchereau, J D Capra, V Pascual
• Journal: European journal of immunology (Eur J Immunol) Vol. 30 Issue 10 Pg. 3039-48 (Oct 2000) ISSN: 0014-2980 [Print] Germany
• PMID: 11069088 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neoplasm Proteins
• RNA, Antisense
• RNA, Messenger
• RNA, Neoplasm
• SERPINA9 protein, human
• Serpins
• CD40 Ligand

Topics

• Alternative Splicing
• Amino Acid Sequence
• B-Lymphocytes (enzymology)
• CD40 Ligand (physiology)
• Chromosomes, Human, Pair 14 (genetics)
• Cloning, Molecular
• Enzyme Induction
• Gene Expression Profiling
• Germinal Center (cytology)
• HL-60 Cells (enzymology)
• Humans
• Molecular Sequence Data
• Neoplasm Proteins (genetics)
• RNA, Antisense (genetics)
• RNA, Messenger (biosynthesis)
• RNA, Neoplasm (genetics)
• Sequence Alignment
• Sequence Homology, Amino Acid
• Serpins (biosynthesis, genetics, isolation & purification)
• Subtraction Technique
• Transcription, Genetic