Differential structure-function requirements of the transmembranal domain of the B cell antigen receptor.
By generating phosphorylcholine (PC)-specific, wild-type (mu), and chimeric (mu-I-A alpha) antigen receptor transfectants of mature B cells, we have shown that the COOH terminus of the mu heavy chain is essential for three major functions: immediate signal transduction (measured as changes in intracellular Ca2+), antigen presentation, and induction of immunoglobulin M secretion. A more detailed analysis of structural requirements of the COOH-terminal domains contributing to these functions was achieved by systematically replacing the spacer, cytoplasmic, and transmembranal domains of the mu-I-A alpha chimeric chain with those of mu. Using this rescue approach, we show that the carboxyl two-thirds of the transmembranal domain (proximal to the cytoplasmic domain) is required for induction of intracellular Ca2+, whereas the complete transmembranal domain is required for the function of antigen presentation but is dispensable for induction of antibody secretion.
Parikh
V S
VS
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Bishop
G A
GA
Liu
K J
KJ
Do
B T
BT
Ghosh
M R
MR
Kim
B S
BS
Tucker
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D007075:Immunoglobulin M / Q000378:metabolism; D016393:Lymphoma, B-Cell; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010767:Phosphorylcholine / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013329:Structure-Activity Relationship; D014162:Transfection
D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D010767:Phosphorylcholine; D002118:Calcium