DeltaBAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF.
The tumor necrosis family member BAFF is limiting for the survival of follicular B lymphocytes, but excessive BAFF signaling can lead to autoimmunity, suggesting that its activity must be tightly regulated. We have identified a conserved alternate splice isoform of BAFF, called deltaBAFF, which lacks 57 nt encoding the A-A1 loop and is co-expressed with BAFF in many mouse and human myeloid cells. Mouse deltaBAFF appears on the plasma membrane, but unlike BAFF it is inefficiently released by proteolysis. DeltaBAFF can associate with BAFF in heteromultimers and diminish BAFF bioactivity and release. Thus, alternative splicing of the BAFF gene suppresses BAFF B cell stimulatory function in several ways, and deltaBAFF may promote other functions as well.
Gavin
Amanda L
AL
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. agavin@scripps.edu
Aït-Azzouzene
Djemel
D
Ware
Carl F
CF
Nemazee
David
D
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012190:Retroviridae / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000737:chemistry*
D053264:B-Cell Activating Factor; D018076:DNA, Complementary; D004220:Disulfides; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha