The unique and immunoglobulin-like regions of surrogate light chain component l5 differentially interrogate immunoglobulin heavy-chain structure

• Published in: Molecular immunology Vol. 47; no. 6; pp. 1195 - 1206
• Main Authors: Smith, Brendan P, Roman, Christopher AJ
• Format: Journal Article
• Language: English
• Published: 01.03.2010
• ISSN: 0161-5890
• DOI: 10.1016/j.molimm.2010.01.002

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 l-like SLC vets billions of unique V sub(H) domains for compatibility with polymorphic [kappa] and l L chains is unclear, because the SLC is composed of not only the Ig domains of VpreB and l5, 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 l5 to H chain screening by evaluating the preBCR-forming capability of l5 mutants with a diverse panel of H chains. Using transformed mouse B cells, we demonstrate that the Ig domain of l5 was sufficient and its UR dispensable for the rejection of V sub(H)Q52 and V sub(H)10 SLC-incompatible H chains. In contrast, the l5 UR was necessary to discriminate between SLC-incompatible and -compatible V sub(H)81X H chains. Substituting the Ig domains of l5 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, l5 differentially relies on the l-like Ig and UR to probe H chain structure to best accommodate diversity among H chains.