HISTOGENESIS OF CD5-POSITIVE AND CD5-NEGATIVE B-CELL NEOPLASMS ON THE ASPECT OF SOMATIC MUTATION OF IMMUNOGLOBULIN HEAVY CHAIN GENE VARIABLE REGION

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The immunoglobulin heavy chain (IgH) gene of B-cells dramatically alters twice in their differentiation to memory or plasma cells; VDJ recombination at B-cell precursor and somatic hypermutation, class switch recombination and receptor revision at germinal center (GC) B-cells. Among them, somatic hypermutation of the IgH gene variable region (VH gene) is a powerful tool for detection of B-cell differentiation. B-cells and B-cell neoplasms have been divided into following ; 1) pre-GC B-cells and neoplasms with a germline VH gene and 2) GC and post-GC B-cells and neoplasms with a somatically mutated VH gene. In this article, we review normal B-cell differentiation and histogenesis of various types of B-cell neoplasms on the aspect of somatic mutation of the rearranged VH gene. In particular, differences between CD5⁺ and CD5⁻ B-cell neoplasms, using our own data of over 100 cases with B-cell neoplasms, are discussed. Although CD5⁺ B-cells are included in pre-GC B-cells for the reason of germline VH gene in most of CD5⁺ Bcells, an about 5% of CD5⁺ B-cells show somatically mutated VH gene. The rearranged VH gene of CD5⁺ B-cell neoplasms shows heterogeneity, whereas CD5⁻ B-cell neoplasms possess somatically mutated VH gene with a mean of 8∼12%. Both CD5⁺ B-cell chronic lymphocytic leukemia and CD5⁺ diffuse large B-cell lymphoma display that about half of cases show a germline or low frequency of somatic mutation and the others possess somatically mutated VH gene. CD5⁺ mantle cell lymphoma constitutes most cases with germline and a small number of cases with mutated VH gene. Therefore, CD5⁻ B-cells & CD5⁻ B-cell neoplasms are distinct from CD5⁺ B-cells and CD5⁺ B-cell neoplasms in somatic mutation of VH gene. It suggests that each of CD5⁻ and CD5⁺ B-cells independently has its own differentiation.