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

［Review Article］

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

NAOYA NAKAMURA and MASAFUMI ABE

Department of Pathology I, Fukushima Medical University
School of Medicine, Fukushima

(Received May 12, 2003, accepted May 27, 2003)

Abstract: 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⁺ B-cells, 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.

Key words: immunoglobulin heavy chain gene, somatic mutation, PCR, B-cell, lymphoma, CD5

中村直哉，阿部正文

Correspondence to: Naoya Nakamura, Department of Pathology, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan.
E-mail: nao@fmu.ac.jp