Germinal center-like B cells in inflamed tissues 

B cell activation and differentiation normally takes place in secondary lymphoid organs. However, under inflammatory conditions, B cells are frequently found in inflamed non-lymphoid tissues where they substantially contribute to tissue destruction by production of antibodies and pro-inflammatory chemokines. We now could show that B cells in the tissue do not only exert effector functions but that the inflamed tissue is a site of active B cell differentiation taking place outside secondary or tertiary lymphoid tissues.

We have developed a murine airway inflammation model which allows to track and analyze antigen-specific B and T cells simultaneously in lung-draining lymph node and inflamed lung tissue. In the inflamed lung, we identified two novel B cell populations of either Bcl-6⁺ germinal center-like or T-bet⁺ CXCR3⁺ inflammatory B cells located outside ectopic lymphoid tissue. Our data indicate that germinal center-like B cells locally differentiate in contact with follicular helper-like T cells, hypermutate their B cell receptor, and give rise to local antibody-producing cells.

In this project, we will further define the phenotype and function of tissue-infiltrating B cells in comparison to classical germinal center B cells in secondary lymphoid organs. To answer the question how B cell differentiation can take place outside of the ordered structure of the germinal center, we will analyze the composition and micro-environment of lung infiltrates. To track the migratory behavior and the interaction of lung-infiltrating B cells with other cell types, a micro-bronchoscopic in vivo imaging technique will be established. We will also functionally analyze factors like T-bet, CXCR3, and different chemokines regarding their role in B cell migration into the tissue, generation of a local inflammatory micro-environment, and for the generation of germinal center-like B cells in the tissue.

Since B cells in inflamed tissues represent a significant proportion of all antigen-specific B cells, a better understanding of their commonalities and differences compared to B cells in secondary lymphoid organs will be important for all B cell-targeted therapies.