Antibody molecules produced by B cells are engaged in the humoral immunity. Antibodies have molecular diversity to respond specifically to each of innumerable species of antigen. Antibody molecular diversity is the immediate result of immunoglobulin gene diversity which is formed by complicated processes including VDJ rearrangement and is thought to reflect differentiation status of B cells. Somatic mutation occurs in these immunoglobulin genes after main VDJ rearrangement and also plays an important role in further widening of molecular diversity.
In recent years, the significance of somatic mutation of immunoglobulin gene in B-cell differentiation process was made clear, and as the result, identification of the normal counterpart of tumor cells became possible on gene level studies, which had been judged mainly from histocytological and immunohistochemical studies.

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The t (11; 18) (q21; q21) translocation is a characteristic chromosomal aberration in lowgrade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3 encompassing the breakpoint at 18q21 in MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. We further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from the BAC 193f9. The breakpoints at 18q21 in three of the five MALT patients were found to be clustered within approximately 20kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of five MALT lymphoma patients. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation is strongly suggested to play an importance role in the development of MALT lymphoma.

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The t (9; 14) (p13; q32) chromosomal translocation is specifically observed in B-cell malignancies such as approximately an half of lymphoplasmacytic lymphoma (LPL) and a small fraction of diffuse large B-cell lymphoma (DLBCL). It results in the juxtaposition of PAX-5 gene, which encodes for an essential transcription factor (BSAP: B-cell lineage specific activator protein) for B-cell development, to the Ig heavy chain gene (IgH) locus. Deregulated expression of the PAX-5 gene as a consequence of this alteration is assumed to lead to the transformation of the B cells at the lymphoplasmacytic stages, although the mechanisms involved in this process remain unknown. A diagnostic procedure using FISH (fluorescence in situ hybridization), which is capable of detecting 80% of the widely scattering 9p13 breakpoints involved in this translocation, was also developed. Thus, further accumulation of the LPL cases and the understanding of the physiological and the pathological roles of the PAX-5 gene in B-cell development may lead to the establishment of the optimal clinical treatment strategy for LPL and LPL-derived DLBCL cases.

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Chromosomal translocations involving 3q27 were found with non-Hodgkin's lymphomas of diffuse large cell type. The low frequency of bone marrow infiltration and high incidence of extranodal involvement were suggested. There have been the conflicting results concerning the prognosis of the patients with the BCL6 rearrangements. A 36 year old male patient with gastric lymphoma was described. He received subtotal gastrectomy and adjuvant chemotherapy. Although he could achieve complete remission, he relapsed at the cervical lymph node swelling eight years later. The 3q27 translocations are unique in that this locus translocate to not only the immunoglobulin genes (IGH, IGK, IGL) but also to non-random variable translocation partners. This case indicates the significance of der (3) than der (2) for tumor cells to gain growth advantage.

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