Precursor B cell receptor signaling activity can be uncoupled from surface expression.
Signals from the precursor BCR (preBCR) cause proliferation and differentiation of progenitor (pro-) B cells into pre-B cells. Given the very low amounts of surface preBCRs and the demonstrated cell autonomy of preBCR signaling, we examined the possible occurrence of preBCR signal propagation from intracellular membranes such as the endoplasmic reticulum (ER) and the trans-Golgi network (TGN) in transformed and primary pro-B cells. PreBCRs composed of normal Ig mu or truncated Dmu heavy chains (HCs) were redirected to intracellular sites via localization sequences appended to the HC cytoplasmic tail. PreBCR complexes retained in the TGN or shunted from the TGN to lysosomes were as or 50% as active as the corresponding wild-type preBCRs in directing preBCR-dependent events, including CD2 and CD22 expression and proliferation in primary pro-B cells. This occurred despite their low to undetectable surface expression in transformed cells, which otherwise allowed significant surface accumulation of wild-type preBCRs. In contrast, ER-retained preBCRs were inactive. These results suggest that preBCR signaling is remarkably tolerant of dramatic changes in its subcellular distribution within post-ER compartments and support the possibility that the preBCR can activate signaling pathways in the TGN as well as the plasma membrane.
Guloglu
F Betul
FB
School of Graduate Studies, Program in Molecular and Cellular Biology, State University of New York-Downstate Medical Center at Brooklyn, NY 11203, USA.
Roman
Christopher A J
CA
D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D007425:Intracellular Membranes / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism
D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell