The extracellular membrane-proximal domain of human membrane IgE controls apoptotic signaling of the B cell receptor in the mature B cell line A20.
Ag engagement of BCR in mature B cells can deliver specific signals, which decide cell survival or cell death. Circulating membrane IgE+ (mIgE+) cells are found in extremely low numbers. We hypothesized that engagement of an epsilonBCR in a mature isotype-switched B cell could induce apoptosis. We studied the role of the extracellular membrane-proximal domain (EMPD) of human mIgE upon BCR engagement with anti-Id Abs. Using mutants lacking the EMPD, we show that this domain is involved in controlling Ca2+ mobilization in immunoreceptors of both gamma and epsilon isotypes, as well as apoptosis in signaling originated only from the epsilonBCR. We mapped to the epsilonCH4 ectodomain the region responsible for apoptosis in EMPD-deleted receptors. Ca2+ mobilization was not related to apoptotic signaling. This apoptotic pathway was caspase independent, involved ERK1/2 phosphorylation and was partially rescued by CD40 costimulation. We therefore conclude that the EMPD of human mIgE is a key control element of apoptotic signaling delivered through engagement of epsilonBCR within the context of a mature B cell.
Poggianella
Monica
M
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Bestagno
Marco
M
Burrone
Oscar R
OR
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D005110:Extracellular Space / Q000737:chemistry / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D007073:Immunoglobulin E; D002118:Calcium