Background Basophil granulocytes (basophils) are rare immune cells representing less than 1% of circulating leukocytes. They are classically known as important players in allergy and helminth infections. However, recent studies also indicate a role in autoimmune disease including systemic lupus erythematodes (SLE). In a murine model of SLE binding of self-reactive IgE to basophils induced their homing to lymph nodes and subsequently enhanced production of self-reactive autoantibodies in reaction to basophil derived Th2 cytokines (1). In addition, murine basophils were shown to enhance immunological memory B cell responses and plasma cell survival (2) suggesting direct or indirect interaction between B cells and basophils. However, most data were obtained in the mouse system and data about human basopohil/B cell interaction are rare.
Objectives We therefore hypothesize that human basophils and B cells interact, and that this interaction can be disturbed in autoimmune diseases such as SLE.
Methods Human basophils and B cells were isolated from peripheral blood of healthy individuals and co-cultured in vitro. B cell survival and proliferation as well as generation of plasma cells were determined by flow cytometry and cell counting. For investigation of antibody production ELISA and ELISPOT were performed.
Results Our data demonstrate that human basophils significantly support B cell survival and proliferation. In response to stimulation with the TLR9 agonist CpG the number of CD138 expressing mature plasma cells w significantly increased in the presence of basophils. Moreover, plasma cells produced significantly more immunoglobulin M, A and G when basophils were present in the co-culture system. Our studies suggest that BAFF might be involved in these processes. Currently, we are further investigating the mechanism involved in this interaction and if it is disturbed in patients with SLE.
Conclusions We conclude that human basophils and B cells interact resulting in enhanced B cell immune responses. This interaction may also impact the pathogenesis and most importantly auto-antibody production in SLE.
Charles N, Hardwick D, Daugas E, Illei GG, Rivera J. Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat Med 2010; 16:701-7.
Denzel A, Maus UA, Rodriguez Gomez M, Moll C, Niedermeier M, Winter C, et al. Basophils enhance immunological memory responses. Nat Immunol 2008; 9:733-42.
Acknowledgements This work was supported by the German Research Foundation (DFG ME19372313 and DI1930/1-1).
Disclosure of Interest None declared