A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses.

Area of Science:

• Immunology
• Microbiology

Background:

• The compartmentalization of immune responses against gut flora in mucosal tissues during homeostasis is debated.
• Understanding the generation and persistence of systemic immune cells responding to gut microbiota is crucial.

Purpose of the Study:

• To investigate the generation and characteristics of systemic memory B cell subsets in response to gut flora without deliberate immunization.
• To determine the origin and maintenance mechanisms of these systemic B cells.

Main Methods:

• Utilized an inducible AID (Activation-Induced Cytidine Deaminase) fate-mapping mouse model.
• Analyzed B cell subsets (IgM+, IgA+) in spleen, bone marrow, and mucosal tissues.
• Investigated clonal relationships, renewal kinetics after anti-CD20 treatment, and B cell reactivity.

Main Results:

• Generated systemic memory B cell subsets, including splenic IgM+ B cells and IgA+ plasma cells, in naive mice.
• IgA+ plasma cells depend on gut flora, while IgM memory B cells are generated in germ-free conditions, though reduced.
• Splenic IgM+ memory B cells are sustained by B cell clones from mucosal germinal centers and exhibit reactivity to bacteria and retroviruses.

Conclusions:

• Ongoing B cell activation in gut-associated lymphoid tissues creates a diversified systemic compartment.
• This compartment exhibits long-lasting clonal persistence and provides protective capacity against systemic bacterial infections.