Pre-B cell receptor signaling mediates selective response to IL-7 at the pro-B to pre-B cell transition via an ERK/MAP kinase-dependent pathway.
B lymphocyte development is regulated at multiple checkpoints, mediated by signals originating both inside and outside the cell. Two signaling pathways known to be essential in this process are interleukin-7 (IL-7) and the pre-B cell receptor (pBCR). We have shown previously that these signaling pathways intersect functionally. Specifically, response to low concentrations of IL-7 requires pBCR expression. In this report, we identify the ERK/MAP kinase pathway as a key regulatory component of this response. We propose a molecular mechanism for the selective expansion of pBCR(+) precursors and for the culling of inappropriately rearranged pro-B cells.
Fleming
H E
HE
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Paige
C J
CJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001853:Bone Marrow / Q000196:embryology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D015851:Interleukin-7 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000378:metabolism
D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell; D020395:Receptors, Interleukin-7; D020928:Mitogen-Activated Protein Kinases