THE HUMAN PRE-B-CELL RECEPTOR - STRUCTURAL CONSTRAINTS FOR A TENTATIVE MODEL OF THE PSEUDO-LIGHT (PSI-L) CHAIN

In human pre-B cells, the mu chain is associated with a surrogate ligh t chain composed of the lambda-like and Vpre-B gene products. This pre -B cell receptor presumably triggers early steps of B cell differentia tion. We have determined the NH2-terminal amino acid sequence of the l ambda-like chain, showing that the mature chain results from the cleav age of a leader segment of 44 residues, leaving a polypeptide of 169 a mino acids having partial features of the Ig light chain domains, with the exception of the first 50 amino acid NH2-terminal region. We have completed the nucleotide sequence of the Vpre-B gene, which appears t o contain 126 residues in its mature form of which the 24 COOH-termina l portion was not Ig-related. Analysis of transfectants has provided d irect evidence that lambda-like and Vpre-B chains assemble together ev en in the absence of heavy chain, prompting the search for a structura l basis of this interaction. Comparison with the domain organization o f the regular Ig lambda chain suggests that most of the Psi L chain ca n be accommodated within a CL-VL-like structure, with an extra ''subdo main'' contributed by the non-Ig-like portions of both the lambda-like and Vpre-B polypeptides.