Functional Immunoglobulin Light Chain Genes

Rearrangement of Ig genes proceeds during B cell differentiation in an orderly fashion. First the heavy (H) chain gene is rearranged in pre-B cells . These cells can express cytoplasmic A chain but no light (L) chain (1). The K light chain genes rear range next and if they fail to produce a functional gene on either chromosome the X light chain genes are rearranged (2) . It is generally believed that the expression of an Ig molecule on the cell surface triggers a feed-back mechanism that shuts off the rearrangement process (3, 4) . Continuous rearrangement of light chain genes has been reported in some pre-B cell lines transformed with Abelson murine leukemia virus (A-MuLV)' (5) . Nevertheless, mature B cells that express surface Ig (sIg+) generally maintain their functionally rearranged Ig genes and remain committed to express antibodies composed of those same H and L chains . Here we show that a sIg+ B cell can alter its surface receptor by continuing to rearrange its K light chain locus . We have previously isolated Ig variants (6) of 38C13, a carcinogen-induced murine B cell lymphoma (7) . These variants arose in tumor-bearing animals that were treated with antiidiotypic mAbs. Although a high percentage of the animals were cured, some developed tumors despite the therapy. Analysis of the variant cells revealed that they expressed sIg but failed to react with the antiidiotypic antibody. mAbs were produced that could discriminate between the Ig produced by the parental tumor and by each ofthe variants . Further analysis showed that the Ig protein expressed by the variants contained identical heavy chains but differed in their light chains . Southern blot analysis showed identical rearrangements at the H chain locus and established that the variants were clonally related . However, the variants differed from each other in their L chain gene rearrangement patterns . The Ig V region genes expressed by these variants were cloned and sequenced . As expected, the VH genes were identical in all variants and in the parental 38C13