NDLI: The survival and differentiation of pro-B and pre-B cells in the bone marrow is dependent on IL-7R Tyr449.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Patton, Daniel T. Plumb, Adam W. Abraham, Ninan
Description	Author Affiliation: Patton DT ( Infection, Inflammation and Immunity Research Group, Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Plumb AW ( Infection, Inflammation and Immunity Research Group, Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Abraham N ( Infection, Inflammation and Immunity Research Group, Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada)
Abstract	IL-7 is critical for murine T and B cell development and survival and plays a significant role in lymphoblastic leukemia in both humans and mice. We evaluated the role of the IL-7R Tyr(449) cytoplasmic SH2-binding motif in IL-7-mediated B cell development using a knock-in mouse with a Tyr to Phe mutation (IL-7R (449F/449F) mouse). IL-7R (449F/449F) and IL-7R (-/-) mice showed no defect in the number of pre-pro-B cells, although IL-7R (449F/449F) mice had decreased Ebf1 in pre-pro-B cells and impairment in B cell-committed CLPs. We identified that IL-7R Tyr(449) was critical for both pro-B and pre-B stages of development in the bone marrow. IL-7R (449F/449F) and IL-7R (-/-) mice had comparable precursor B cell defects, indicating that signaling from the IL-7R required this motif. Although the defect in IL-7R (449F/449F) pro-B cells was associated with loss of STAT5 activation and diminished expression of Mcl1, this was not rescued by overexpression of Bcl-2. IL-7R (449F/449F) and IL-7R (-/-) pre-B cells also showed defective cyto-Igµ and CD25 expression, associated with reduced levels of Rag1, Rag2, and Irf4. Pre-B cells from IL-7R (449F/449F) mice also failed to proliferate, perhaps as a result of the failure to rearrange Igµ. Our data suggest that IL-7R Tyr(449) was essential for IL-7R signaling in bone marrow B cell development and survival.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bone Marrow Immunology Cell Differentiation Mutation, Missense Precursor Cells, B-lymphoid Receptors, Interleukin-7 Signal Transduction Amino Acid Substitution Animals Genetics Cell Proliferation Cell Survival Dna-binding Proteins Gene Rearrangement, B-lymphocyte Homeodomain Proteins Immunoglobulin Mu-chains Interferon Regulatory Factors Interleukin-2 Receptor Alpha Subunit Mice Mice, Knockout Myeloid Cell Leukemia Sequence 1 Protein Cytology Proto-oncogene Proteins C-bcl-2 Stat5 Transcription Factor Tyrosine Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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