Researchers have found that gut bacteria exert a dramatic effect on the development of the immune system’s B lymphocytes (a type of white blood cell that produces antibodies) in mice. The study is the first to document early B cell development in the gut, as well as microbes’ influence on this process.
Immature B cells shuffle antibody gene segments to create a vast antibody repertoire. This shuffling process—called V(D)J recombination—relies on a factor called RAG. V(D)J recombination programs each B cell to make just one kind of antibody that will work against a single antigen. Due to the random shuffling process, some B cells make self-reactive receptors. If this happens, the cells continue the RAG-mediated shuffling which replaces a self-reactive receptor with one that is not self-reactive.
The researchers also noted that immature B cells within a part of the gut called the lamina propria were actively shuffling antibody genes. The level of gene shuffling within gut B cells was similar to B cells developing in the bone marrow, suggesting there was also primary B cell development in the gut.
According to the researchers, the gut might be another location for primary B cell development in the mouse in addition to the bone marrow. Moreover, the researchers saw that the diversity of the primary B cell repertoire in the gut differed from that in the bone marrow. The level of shuffling was the same, but the nature of the actual rearrangements differed dramatically between the two sites.
“Overall, our study suggests that gut microbes not only regulate T cell activities but also influence those of developing B cells,” said Duane R. Wesemann, MD, PhD, Division of Rheumatology, Allergy and Immunology, BWH Department of Medicine, lead study author.
The study was published online August 21, 2013, in Nature.