title: CD74 induces TAp63 expression leading to B-cell survival.
abstract: Most mature follicular B cells circulate within the periphery in a quiescent state, without actively contributing to an acute immune response. Lasting B-cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. We recently demonstrated that cell surface CD74 controls mature B-cell survival. Stimulation of cell surface CD74 leads to NF-kappaB activation, which enables entry of the stimulated B cells into the S phase, induction of DNA synthesis, and cell division, and augments the expression of survival genes. In the present study, we investigated CD74 target genes to determine the identities of the molecules whose expression is modulated by CD74, thereby regulating B-cell survival. We report that CD74 activates the p65 member of the NF-kappaB family, which in turn up-regulates the expression of p53-related TAp63 proteins. TAp63 then binds and transactivates the Bcl-2gene and induces the production of Bcl-2 protein, thereby providing the cells with increased survival capacity. Thus, the CD74/NF-kappaB/TAp63 axis defines a novel antiapoptotic pathway in mature B cells, resulting in the shaping of both the B-cell repertoire and the immune response.
authors.affiliation: Departments of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Frida
authors.initials: F
authors.lastname: Lantner
authors.forename: Diana
authors.initials: D
authors.lastname: Starlets
authors.forename: Yael
authors.initials: Y
authors.lastname: Gore
authors.forename: Liat
authors.initials: L
authors.lastname: Flaishon
authors.forename: Ayala
authors.initials: A
authors.lastname: Yamit-Hezi
authors.forename: Rivka
authors.initials: R
authors.lastname: Dikstein
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Yossy
authors.initials: Y
authors.lastname: Machluf
authors.forename: Moshe
authors.initials: M
authors.lastname: Oren
authors.forename: Idit
authors.initials: I
authors.lastname: Shachar
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology*; D002470:Cell Survival; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D051996:Transcription Factor RelA; C486419:Trp63 protein, mouse; C045084:invariant chain