Microbiota-initiated antibody formation in mice

Microbiota-initiated antibody formation in mice

During an antibody response, immunoglobulin (Ig) in antigen-naïve mature B cells can undergo class-switch recombination (CSR), a switch from one form of Ig to another. CSR enables diversification of antibody functions. CSR to IgD is rare and regulated differently, compared with other Ig CSR events.

Researchers investigated the regulation of IgD CSR in mice. The authors found that deficiency of the DNA damage-response protein 53BP1 caused age-dependent overproduction of IgD in mice with a Trp53bp1 gene mutation.

The IgD overproduction in Trp53bp1-/- mice resulted from increased IgD CSR exclusively within B cells from lymphoid tissues associated with mucous membranes. Gnotobiotic techniques revealed that signals from gut microbiota drove IgD CSR in Trp53bp1-/- mice.

Furthermore, the authors detected microbiota-initiated IgD CSR in lymphoid tissue B cells from the nasal immune system in wild-type mice. By inhibiting alternative nonhomologous end-joining in Trp53bp1-/- mice, the authors found that DNA double-strand breaks in 53BP1-deficient B cells are likely repaired through alternative nonhomologous end-joining as well as homologous recombination pathways, allowing IgD CSR to occur.

According to the authors, the results indicate a pathway in wild-type mice that is hyperactivated in Trp53bp1-/- mice, whereby Toll-like receptor signaling in response to microbiota elicits IgD CSR.