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The Unique Region of Surrogate Light Chain Component 5 Is a Heavy Chain-Specific Regulator of Precursor B Cell Receptor Signaling¹

F. Betul Guloglu^2,*,, Ewa Bajor^2,*,, Brendan P. Smith^*, and Christopher A. J. Roman^3,*

^* Department of Microbiology and Immunology and Program of Molecular and Cellular Biology, School of Graduate Studies, State University of New York, Downstate Medical Center at Brooklyn, Brooklyn, NY 11203

Signals transduced by precursor-BCRs (pre-BCRs) composed of Ig µ heavy chains (HCs) and the surrogate L chain components 5 and VpreB are critical for B cell development. A conserved unique region (UR) of 5 was shown to activate pre-BCR complexes in transformed cells and to engage putative ligands, but its contribution to pre-B cell development is not known. It is also not clear why the -like sequences in 5 are used to select HCs that will associate mainly with L chains. In this study, we show that, in transformed and primary mouse B cell progenitors, receptors containing full-length HCs and lacking the 5UR were expressed at higher surface levels, but exhibited reduced activity compared with normal pre-BCRs in supporting developmental changes that accompany the progenitor to pre-B cell transition in primary cell culture systems and in the bone marrow in vivo. In contrast, deletion of the 5UR did not change net signaling output by the Dµ-pre-BCR, a developmentally defective receptor that exhibited impaired activity in the primary cell culture system. Moreover, the -like sequences in 5 were more accommodating than in supporting surface expression and signaling by the different HCs. These results show that the 5UR is important, although not essential, for surrogate L chain-dependent receptor signaling in primary cells, and furthermore may help allow discrimination of signaling competency between normal and Dµ-pre-BCRs. That the -like portion of 5 in the absence of the UR was nondiscriminatory suggests that the 5UR focuses pre-BCR-dependent selection on the HC V region.

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