#somatic hypermutation

[nkhealth]

Researcher profile: Reiko Shinkura

Professor, Laboratory of Immunology and Infection Control, The University of Tokyo

Mechanisms of gut microbial regulation by intestinal IgA

Outline of research (from Professor Shinkura’s website)

“The immune response has evolved to protect us from pathogenic infectious agents and toxic foreign substances. In acquired immune response, antigen stimulation of B cells induces two distinct genetic alterations in the immunoglobulin (Ig) loci: somatic hypermutation (SHM) and class switch recombination (CSR), both of which require an enzyme, activation-induced cytidine deaminase (AID). After these processes, among diversified Ig repertoire, selected high-affinity Igs efficiently defend host. AID plays a crucial role in host defense but it introduces DNA cleavage into Ig loci and aberrantly into non-Ig loci causing lymphoma. Our aim is to answer ‘how AID’s activity targets Ig loci specifically’ using AID mutant protein and mutant knock-in mice and to understand the precise molecular mechanism of SHM and CSR.

Recently dysbiosis (gut commensal microbial imbalance) is frequently reported to be associated with illnesses such as inflammatory bowel disease (IBD), obesity, cancer, etc. We found that the high-affinity intestinal IgA produced by SHM is important to control non-pathogenic gut bacteria as well as pathogens. Our main question is how intestinal IgA recognizes and targets a huge variety of gut bacteria. We have isolated a useful monoclonal IgA to modulate gut microbiota leading to symbiosis (balanced host-microbial relationship in gut).”

Website

http://www.cbms.k.u-tokyo.ac.jp/english/lab/shinkura.html

[lostdiary-blog]

Somatic Hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (for example, microbes). Somatic hypermutation diversifies B cell receptors used to recognize foreign elements (antigens).

Somatic Hypermutation involves a programmed process of mutation affecting the variable regions of immunoglobulin genes. SHM affects only individual immune cells, and the mutations aren’t transmitted to offspring. Immunoglobulin  An antibody, also known as immunoglobulin is a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as viruses and bacteria. The antibody recognizes a unique part of the foreign target called an antigen (see below).  Each tip of the “Y” of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. The production of the antibodies is the main function of the humoral immune system. 

Antigens In immunology an antigen is a substance that evokes the production of one more antibodies (see above). Each antibody binds to specific antigen by away of an interaction similar to the fit between lock and a key. The substance may be from the external environment or formed within the body. The immune system will try to destroy or neutralize any antigen that is recognized as a foreign and potentially harmful invader.