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The Journal of Immunology, 2001, 167: 3846-3857.
Copyright © 2001 by The American Association of Immunologists

Conventional and Surrogate Light Chains Differentially Regulate Ig µ and Dµ Heavy Chain Maturation and Surface Expression1

Terry Fang, Brendan P. Smith and Christopher A. J. Roman2

Department of Microbiology and Immunology and Morse Institute for Molecular Genetics, State University of New York-Downstate Medical Center, Brooklyn, NY 11203

Positive selection of precursor (pre-) B cells by Ig membrane µ H chains (µm HC) and counterselection mediated by the truncated HC Dµ depend on the ability of each HC to form a pre-B cell receptor (pre-BCR) signaling complex with the surrogate L chain (SLC) components {lambda}5 and Vpre-B. To better understand how pre-BCR signaling output is determined by its Ig components and the SLC, we investigated the regulation of pre-BCR surface expression and HC secretory maturation in a new nonlymphoid system. We took this approach as a means to distinguish B-lineage-specific effects from pre-BCR-intrinsic properties that may influence these aspects of pre-BCR homeostasis necessary for signaling. As in pre-B cells, the SLC in nonlymphoid cells supported only a limited degree of µm HC maturation and low pre-BCR surface expression levels compared with conventional LCs, indicating that this was due to an intrinsic property of the SLC. We identified the non-Ig region of {lambda}5 as harboring the restrictive activity responsible for this phenotype. This property of {lambda}5 was also evident with Dµ, but the overall SLC- and L chain-dependent requirements for Dµ maturation and surface expression were markedly different from those for µm. Surprisingly, Dµ was modified in an unusual manner that was only dependent on Vpre-B. These results establish a novel function of {lambda}5 in limiting surface pre-BCR levels and reveal biochemical properties of Ig molecules that may underlie the diverse consequences of pre-BCR signaling in vivo by different HCs.




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