Conventional and surrogate light chains differentially regulate Ig mu and Dmu heavy chain maturation and surface expression.
Positive selection of precursor (pre-) B cells by Ig membrane mu H chains (mum HC) and counterselection mediated by the truncated HC Dmu 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 lambda5 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 mum 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 lambda5 as harboring the restrictive activity responsible for this phenotype. This property of lambda5 was also evident with Dmu, but the overall SLC- and L chain-dependent requirements for Dmu maturation and surface expression were markedly different from those for mum. Surprisingly, Dmu was modified in an unusual manner that was only dependent on Vpre-B. These results establish a novel function of lambda5 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.
Fang
T
T
Department of Microbiology and Immunology and Morse Institute for Molecular Genetics, State University of New York-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Smith
B P
BP
Roman
C A
CA
D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006026:Glycoside Hydrolases / Q000737:chemistry; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000502:physiology; D007133:Immunoglobulin Joining Region / Q000502:physiology; D007147:Immunoglobulin Light Chains / Q000502:physiology*; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains / Q000502:physiology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D013234:Stem Cells / Q000276:immunology; D014162:Transfection
D007127:Immunoglobulin Constant Regions; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D006026:Glycoside Hydrolases