Molecular basis of the cell-surface expression of immunoglobulin mu chain without light chain in human B lymphocytes.

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Abstract
Four distinct human B-lymphoid cell lines possess the ability to circumvent the mechanism regulating intracellular transport of immunoglobulin protein. These cells do not produce light chains, yet they express .mu. heavy chains on the cell surface at comparable levels to B-cell lines that produce native forms of both proteins. The .mu.-chain mRNA produced all four cell lines was found to contain an identical deletion of most of the heavy-chain variable (VH) region (75% of the 3'' portion), with no apparent alteration in constant (C) region structure. The truncated .mu. (.mu.*)-chain mRNA in these cells was created through the use of a cryptic splice donor site found within the human VH gene(s) utilized by these B-cell lines. The truncated .mu.* chains exhibited a decreased ability to associate with the intracellular transport regulatory protein, heavy-chain binding protein (BiP). This result indicates that VH region structure, in addition of C.mu.1 region structure, influences the formation of the BiP recognition site on the heavy chain. Furthermore, it suggests that the mechanism allowing for cell-surface expression of the .mu.* chains in the absence of light-chain pairing is the inability of BiP to bind to the .mu.* chains and hence prevent their intracellular transport. The high frequency with which the .mu.-only surface immunoglobulin positive phenotype is present in our collection of human B-cell lines and the isolation of one of the cell lines from a healthy individual also suggest that B cells of this type may represent a significant subpopulation among the normal human B-cell repertoire.