title: Tyrosine kinase c-Abl regulates the survival of plasma cells.
abstract: Tyrosine kinase c-Abl plays an important role in early B cell development. Its deletion leads to reduced pro- and pre-B cell generation in mice. However, its function in B cell terminal differentiation remains unexplored. Here, we used c-Ablf/fAicdacre/+mice, in which c-Abl is ablated only in antigen-activated B cells, to study the role of c-Abl in germinal center (GC) B and antibody-secreting plasma cell formation. Upon challenge with a model antigen, we found normal GC and memory B but reduced plasma cells and antigen-specific antibody response in the mutant mice. In-vitro studies revealed that plasma cells lacking c-Abl could be generated but did not accumulate in culture, indicative of survival defect. They also exhibited impaired STAT3 phosphorylation. The plasma cell defects could be rectified by introduction of Bim-deficiency or delivery of colivelin, a STAT3 activator, into c-Ablf/fAicdacre/+mice. Hence, c-Abl signalling regulates the survival of plasma cells.
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, 138668 Singapore.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, 138668 Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117599 Singapore.
authors.forename: Shengli
authors.initials: S
authors.lastname: Xu
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, 138668 Singapore.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, 138668 Singapore.
authors.forename: Xijun
authors.initials: X
authors.lastname: Ou
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, 138668 Singapore.|Department of Microbiology &Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117599 Singapore.
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D056724:Immunity, Humoral; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D010950:Plasma Cells / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000276:immunology / Q000378:metabolism*
chemical_list: D016315:Proto-Oncogene Proteins c-abl