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The Journal of Immunology, 2000, 164: 1961-1970.
Copyright © 2000 by The American Association of Immunologists

Murine Pro-B Cells Require IL-7 and Its Receptor Complex to Up-Regulate IL-7R{alpha}, Terminal Deoxynucleotidyltransferase, and cµ Expression1

Chiju Wei, Richard Zeff and Irving Goldschneider2

Department of Pathology, University of Connecticut Health Center, Farmington, CT 06030

Phenotypic analysis of bone marrow cells from IL-7 knockout (KO) mice revealed that B cell development is blocked precisely at the transition between pro-B cells and pre-B cells. In contrast, the generation of pre-pro-B cells and pro-B cells appeared to be normal, as judged by total cell numbers, proliferative indexes, D-JH and V-DJH gene rearrangements, and mRNA for recombinase-activating gene-1 (RAG-1), RAG-2, TdT, Igµ, {lambda}5, and VpreB. However, upon closer inspection, several abnormalities in pro-B cell development were identified that could be corrected by injection of rIL-7 in vivo. These included the absence of the subset of late pro-B cells that initiates cµ expression for pre-B cell Ag receptor (BCR) formation, and the failure of pro-B cells to up-regulate TdT and the IL-7R{alpha} (but not the common {gamma}-chain) chain. Similar defects were present in common {gamma}-chain and Jak3 KO mice, but not in {lambda}5 or (excluding cytoplasmic Ig µ heavy chain (cµ)) RAG-1 KO mice, all of which also arrest at the late pro-B cell stage. Consequently, up-regulation of TdT and IL-7R{alpha} expression requires signaling through the high affinity IL-7R, but does not require cµ expression or a functional pre-BCR. Taken together, these results suggest that IL-7 and its receptor complex are essential for 1) up-regulating the expression of TdT and IL-7R{alpha}, 2) initiating the production of cµ, and 3) promoting the formation of a functional pre-BCR in/on pro-B cells. These key events, in turn, appear to be prerequisite both for differentiation of pro-B cells to pre-B cells and for proliferation of these cell subsets upon continued stimulation with IL-7.




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