Alternative V kappa gene rearrangements in a murine B cell lymphoma. An explantation for idiotypic heterogeneity.

Abstract

Idiotype variants of 38C13, a murine B cell lymphoma, have been isolated by immunoselection with antiidiotype mAbs. The V region genes for the .kappa. light chains and .mu. heavy chains expressed by these tumor cells were sequenced and compared. There was no evidence for V region somatic point mutation in this tumor. However, while the heavy chain genes were all identical, the light chain genes were all different. The light chain genes of each variant were derived from the V.kappa.-Oxl gene family and joined to J.kappa.4, whereas the light chain gene of the parental tumor was derived from the V.kappa.9 family and joined to J.KAPPA.2. Two of the variants used the identical V.kappa. gene but differed by the inclusion of a variable number of additional nucleotides in the V/J joint. Thus, the idiotypic heterogeneity of this B cell lymphoma arises as a consequence of alternative light chain rearrangements rather than point mutation. This process repetitively uses members of the same V.kappa. gene family. Two of the variants use the identical V.kappa. and J.kappa. gene segments but differ by the presence of extra nucleotides at the V.kappa./J.kappa. joint.