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Germinal centers (GC) are the sites of B cell clonal expansion, somatic hypermutation and clonal selection, a process that leads to the production of antibodies of higher affinity [1](#ref-0001). Efforts have been made to understand the kinetic of events controlling the GC and the production of specific antibodies in protective as well in pathogenic responses, such as autoimmunity and allergy. The ability of newly mutated GC clones to capture and present antigen to T follicular helper cells (Tfh) in the light zone of the GC is crucial for clonal survival and selection. Tfh cells produce IL-21, a key cytokine for the GC reaction and antibody responses [2](#ref-0002). However, it was not understood how IL-21 acts independently on T and B cells to mediate the GC reaction. In this study Quast and colleagues [3](#ref-0003) contribute to elucidate the specific role of IL-21 on the GC reaction and how IL-21 bioavailability affects the outcome of the GC response. They demonstrate that IL-21 influences Tfh cell differentiation and expansion early, before the GC establishment, as well later during GC development, through both autocrine and paracrine mechanisms, regardless of cognate T-B cell interactions.

Multiple sclerosis is an autoimmune disease that affects the central nervous system. Because of its complexity and the difficulty to treat, searching for immunoregulatory responses that reduce the clinical signs of disease by non-aggressive mechanisms and without adverse effects is a scientific challenge. Herein we propose a protocol of oral tolerance induction that prevented and controlled MOG-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The genetically modified strain HSP65-producing Lactococcus lactis was orally administered for 5 consecutive days either before or during disease development in mice. Both protocols of feeding HSP65 resulted in significant reduction in the clinical score of EAE. Frequencies of LAP+CD4+Foxp3- regulatory T cells were higher in spleens and inguinal lymph nodes of fed mice. In addition, intravital microscopy showed that adherence of leukocytes to venules in the spinal cord was reduced in orally treated mice. Oral treatment with HSP65-producing L.lactis prevented leukocytes to leave the secondary lymphoid organs, therefore they could not reach the central nervous system. Despite the inhibition of pathological immune response that drive EAE development, activated T cells were at normal frequencies suggesting that oral tolerance did not induce general immunosuppression, but it led to specific control of pathogenic T cells. Our results indicate a novel therapeutic strategy to prevent and control autoimmune diseases such as multiple sclerosis.