The unique and immunoglobulin-like regions of surrogate light chain component lambda5 differentially interrogate immunoglobulin heavy-chain structure.
PreBCR signaling is critical for B cell development and normally depends on the association of a nascent, component Ig H chain with the surrogate L chain (SLC), which helps ensure that only B cells that synthesize structurally sound antibody can develop. How the invariant and lambda-like SLC vets billions of unique V(H) domains for compatibility with polymorphic kappa and lambda L chains is unclear, because the SLC is composed of not only the Ig domains of VpreB and lambda5, but also the unique regions (URs) that reside at what would be the L chain CDR3. We evaluated the contribution of the Ig and UR domains of lambda5 to H chain screening by evaluating the preBCR-forming capability of lambda5 mutants with a diverse panel of H chains. Using transformed mouse B cells, we demonstrate that the Ig domain of lambda5 was sufficient and its UR dispensable for the rejection of V(H)Q52 and V(H)10 SLC-incompatible H chains. In contrast, the lambda5 UR was necessary to discriminate between SLC-incompatible and -compatible V(H)81X H chains. Substituting the Ig domains of lambda5 with equivalent kappa sequences impaired the SLC's ability to escort all H chains to the surface. Two SLC-incompatible H chains were able to form surface BCRs with two kappa L chains, indicating that the SLC's ability to predict the L chain compatibility of a H chain is not absolute. In sum, lambda5 differentially relies on the lambda-like Ig and UR to probe H chain structure to best accommodate diversity among H chains.
Smith
Brendan P
BP
Program in Molecular and Cellular Biology, School of Graduate Studies, Brooklyn, NY, USA.
Roman
Christopher A J
CA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000276:immunology*; D054444:Immunoglobulin Light Chains, Surrogate / Q000737:chemistry* / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D054420:Pre-B Cell Receptors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D007143:Immunoglobulin Heavy Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D054420:Pre-B Cell Receptors; D011993:Recombinant Fusion Proteins