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A Unique Role for the 5 Nonimmunoglobulin Tail in Early B Lymphocyte Development¹

Christian Vettermann^*, Kai Herrmann^*, Christine Albert^*, Edith Roth^*, Michael R. Bösl and Hans-Martin Jäck^2,*

^* Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen, Erlangen, Germany; and Max-Planck-Institute for Neurobiology, Martinsried, Germany

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 Igµ H chain, surrogate L chain (SLC), and Ig-Igβ, 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 5 is critical for enhancing pre-BCR-induced proliferation signals. Pre-BCRs with a mutated 5 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 5 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 5 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 Igµ H chains.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was financed in part by the Interdisciplinary Center for Clinical Research (IZKF), the research Grants SFB466 and FOR832 (JA968/4) from the Deutsche Forschungsgemeinschaft (DFG) to H.-M.J.; the stipend of K.H. was supported by an intramural ELAN grant and the DFG training Grant GK592.

² Address correspondence and reprint requests to Dr. Hans-Martin Jäck, Division of Molecular Immunology, University of Erlangen-Nürnberg, Glückstrasse 6, D-91054 Erlangen, Germany. E-mail address: hjaeck{at}molmed.uni-erlangen.de

³ Abbreviations used in this paper: HC, H chain; h, human; LC, L chain; LCR, locus control region; µHC, Igµ H chain; m, murine; PI, propidium iodide; pre-, precursor; pro-, progenitor; RPE, R-phycoerithrin; SLC, surrogate L chain; U, unique tail; wt, wild type.

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The JI 2008 181: 2939-2940. [Full Text]  

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