Activation and maturation of antigen-specific B cells in nonectopic lung infiltrates are independent of germinal center reactions in the draining lymph node.

Pulmonary T and B cells are important for protection of this mucosal barrier site. While viral infections lead to the development of ectopic lymphoid structures highly similar to those in germinal centers in secondary lymphoid organs, little is known about how T/B cooperation occurs in the unstructured, diffuse tissue infiltrates characteristic of autoimmune diseases and nonviral infections. Using a mouse model of interstitial lung inflammation, we found that naive B cells are directly activated in lung tissue. Despite the absence of any germinal center-like structures, the interaction of B cells with peripheral T helper cells results in efficient somatic hypermutation and class switching. As antigen-presenting cells, macrophages are critical for this process. Unique B-cell repertoires indicated that the lung response was autonomous from the lung-draining lymph node. Only lung GC-like B cells were switched to IgA and had a broader repertoire, making them ideal candidates for producing broadly neutralizing immunoglobulins against respiratory pathogens.