Tanwar , S. and Dhar, A. and Varanasi, V. and Mukherjee , T. and Boppana, R. and Basak , S. and Bal, V. and George , A. and Rath , S. (2017) Mediation of transitional B cell maturation in the absence of functional Bruton's tyrosine kinase. Scientific Report (7). p. 46029.

Text 74. Dr. Ramanmurthy B. (Scientifc Reports) open access.pdf Download (2328Kb)

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.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	17 Dec 2018 10:09
Last Modified:	19 Feb 2021 06:47
URI:	http://nccs.sciencecentral.in/id/eprint/565

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