title: Mediation of transitional B cell maturation in the absence of functional Bruton's tyrosine kinase.
abstract: X-linked immune-deficient (Xid) mice, carrying a mutation in Bruton's tyrosine kinase (Btk), have multiple B cell lineage differentiation defects. We now show that, while Xid mice showed only mild reduction in the frequency of the late transitional (T2) stage of peripheral B cells, the defect became severe when the Xid genotype was combined with either a CD40-null, a TCRbeta-null or an MHC class II (MHCII)-null genotype. Purified Xid T1 and T2 B cells survived poorly in vitro compared to wild-type (WT) cells. BAFF rescued WT but not Xid T1 and T2 B cells from death in culture, while CD40 ligation equivalently rescued both. Xid transitional B cells ex vivo showed low levels of the p100 protein substrate for non-canonical NF-kappaB signalling. In vitro, CD40 ligation induced equivalent activation of the canonical but not of the non-canonical NF-kappaB pathway in Xid and WT T1 and T2 B cells. CD40 ligation efficiently rescued p100-null T1 B cells from neglect-induced death in vitro. These data indicate that CD40-mediated signals, likely from CD4 T cells, can mediate peripheral transitional B cell maturation independent of Btk and the non-canonical NF-kappaB pathway, and thus contribute to the understanding of the complexities of peripheral B cell maturation.
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Tanwar
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Atika
authors.initials: A
authors.lastname: Dhar
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Vineeth
authors.initials: V
authors.lastname: Varanasi
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Tapas
authors.initials: T
authors.lastname: Mukherjee
authors.affiliation: National Centre for Cell Sciences, Pune, India.
authors.forename: Ramanamurthy
authors.initials: R
authors.lastname: Boppana
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Soumen
authors.initials: S
authors.lastname: Basak
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Bal
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Anna
authors.initials: A
authors.lastname: George
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Rath
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D016328:NF-kappa B; C505720:Tnfsf13b protein, mouse; D018799:Intercellular Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse