Somatic hypermutation (SHM) is linked to leukemia via its alteration of B cell receptor (BCR) autoreactivity

06-23-2006

According to recent research published in the The Journal Of Clinical Investigation, "B cell chronic lymphocytic leukemia (CLL) is a disease of expanding monoclonal B cells whose BCR mutational status defines two subgroups; patients with mutated BCRs have a more favorable prognosis than those with unmutated BCRs. CLL B cells express a restricted BCR repertoire including antibodies with quasi-identical complementarity-determining region 3 (CDR3), which suggests specific antigen recognition."

"The antigens recognized by CLL antibodies may include autoantigens since about half of CLL B cells produce autoreactive antibodies. However, the distribution of autoreactive antibodies between Ig heavy-chain variable-unmutated (IgV-unmutated) CLL (UM-CLL) and IgV-mutated CLL (M-CLL) is unknown," reported M. Herve and associates at the Hospital for Special Surgery in New York.

The scientists explained, "To determine the role of antibody reactivity and the impact of somatic hypermutation (SHM) on CLL antibody specificity, we cloned and expressed in vitro recombinant antibodies from M-and UM-CLL B cells and tested their reactivity by ELISA. We found that UM-CLL B cells expressed highly polyreactive antibodies whereas most M-CLL B cells did not. When mutated nonautoreactive CLL antibody sequences were reverted in vitro to their germline counterparts, they encoded polyreactive and autoreactive antibodies."

"We concluded that both UM-CLLs and M-CLLs originate from self-reactive B cell precursors and that SHM plays an important role in the development of the disease by altering original BCR autoreactivity," wrote Herve's team.

Hervé and colleagues published their study in The Journal Of Clinical Investigation (Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive b cell precursors despite expressing different antibody reactivity. J Clin Invest, 2005;115(6):1636-43).

For additional information, contact M. Hervé, Hospital for Special Surgery, Laboratory of Biochemistry and Molecular Immunology, New York, New York 10021, USA.

Keywords: New York, New York, United States, B Cell Chronic Lymphocytic Leukemia, B Cell Receptor, Biotechnology, Leukemia, Recombinant Technology.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.