Identification of centerin: a novel human germinal center B cell-restricted serpin.
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.
Frazer
J K
JK
UT Southwestern Medical Center at Dallas, TX, USA.
Jackson
D G
DG
Gaillard
J P
JP
Lutter
M
M
Liu
Y J
YJ
Banchereau
J
J
Capra
J D
JD
Pascual
V
V
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000201:enzymology*; D023201:CD40 Ligand / Q000502:physiology; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003001:Cloning, Molecular; D004790:Enzyme Induction; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000166:cytology*; D018922:HL-60 Cells / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification*; D013382:Subtraction Technique; D014158:Transcription, Genetic
D009363:Neoplasm Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C476825:SERPINA9 protein, human; D015843:Serpins; D023201:CD40 Ligand