Lineage and stage specificity of isotype switching in humans

The lineage and stage specificity of human isotype switch recombination was investigated by examining the IgH gene configuration in 61 hemopoietic malignancies representing different stages of B and T cell development. An unexpectedly high frequency (20%) of IgM-producing B cell leukemias and lymphomas had undergone C(H) gene rearrangements and deletions consistent with attempted switch recombination. These C(H) gene alterations were found on productive, non-productive, and 14q⁺ chromosomes. These data support the concept of a non-specific (common) switch recombinase activity that is often ineffective. No evidence of such switch recombination was found in 25 μ^- or μ⁺ pre-B cell leukemias with the single exception of a μ^- pre-B leukemia in which subsets of the cells were producing γ- or α-H chains. The switch recombinase activity may be restricted to the B cell lineage, inasmuch as C(H) gene deletions were not observed in T lineage malignancies.