A unique role for the lambda5 nonimmunoglobulin tail in early B lymphocyte development

The Journal of Immunology : Official Journal of the American Association of Immunologists
Christian VettermannHans-Martin Jäck

Abstract

Precursor BCR (pre-BCR) signaling governs proliferation and differentiation of pre-B cells during B lymphocyte development. However, it is controversial as to which parts of the pre-BCR, which is composed of Igmu H chain, surrogate L chain (SLC), and Igalpha-Igbeta, are important for signal initiation. Here, we show in transgenic mice that the N-terminal non-Ig-like (unique) tail of the surrogate L chain component lambda5 is critical for enhancing pre-BCR-induced proliferation signals. Pre-BCRs with a mutated lambda5 unique tail are still transported to the cell surface, but they deliver only basal signals that trigger survival and differentiation of pre-B cells. Further, we demonstrate that the positively charged residues of the lambda5 unique tail, which are required for pre-BCR self-oligomerization, can also mediate binding to stroma cell-associated self-Ags, such as heparan sulfate. These findings establish the lambda5 unique tail as a pre-BCR-specific autoreactive signaling motif that could increase the size of the primary Ab repertoire by selectively expanding pre-B cells with functional Igmu H chains.

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Citations

May 9, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marko KnollKazuo Ohnishi
Apr 26, 2014·Frontiers in Immunology·Keith M HamelMarcus R Clark
Mar 8, 2019·The Biochemical Journal·Georg Petkau, Martin Turner
Aug 29, 2009·European Journal of Immunology·Roxane TussiwandAntonius G Rolink
Aug 24, 2010·Immunological Reviews·Christian Vettermann, Mark S Schlissel
Aug 23, 2012·Scandinavian Journal of Immunology·N Almqvist, I-L Mårtensson
Apr 28, 2010·FEBS Letters·Inga-Lill MårtenssonAngelina I Bernardi
Sep 2, 2015·The Journal of Experimental Medicine·Gina J FialaWolfgang W A Schamel
Jul 10, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dan Eilat, Matthias Wabl
Dec 20, 2018·Frontiers in Immunology·Nicholas GiovannoneCharles J Dimitroff
Apr 2, 2010·Trends in Immunology·Christian Vettermann, Hans-Martin Jäck
Aug 31, 2010·Molecular Immunology·Joseph HaimovichNurit Hollander

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