Abstract
The production of antibody-secreting plasma cells and memory B cells requires the interaction of T follicular helper (Tfh) cells with B cells in the follicle and is modulated by T follicular regulatory (Tfr) cells. We compare the effects of Tfr cells in an in vitro model of bystander Tfh function in the absence of BCR engagement and in a model in which mimics cognate T-B interactions in which the BCR is engaged. In the absence of Tfr cells, Tfh cells from primed mice induce naive B cell differentiation into GC B cells and class switch recombination (CSR) in the presence of anti-CD3 alone or anti-CD3/IgM in a contact-dependent manner. Addition of primed Tfr cells efficiently suppressed GC B cell proliferation, differentiation and CSR in the anti-CD3 alone cultures, but only moderately suppressed BCR-stimulated B cells. When stimulated with anti-CD3 alone, IL-4 is critical for the induction of GC B cells and CSR. IL-21 plays a minimal role in GC B cell differentiation, but a greater role in switching. When the BCR is engaged, IL-4 is primarily required for switching and IL-21 only modestly affects switching. CD40L expression was critical for Tfh-mediated B cell proliferation/differentiation in the absence of B cell engagement. When the BCR was engaged, proliferation of CD40 deficient B cells was partially restored, but was susceptible to suppression by Tfr. These studies suggest that in vitro Tfr suppressor function is complex and is modulated by BCR signaling and CD40-CD40L interactions.
Highlights
A crucial aspect of T-cell dependent immunity is the formation of the germinal center (GC) within the B cell follicles of secondary lymphoid organs
To characterize the role of T follicular helper (Tfh) cells in promoting B cell proliferation and differentiation in vitro, e450-labeled naïve B cells were co-cultured at a ratio of 2:1 with purified Tfh or naïve T (nvT) cells in the presence of antiCD3 or anti-CD3/anti-IgM for 3 d. nvT cells were unable to induce Naïve B (nvB) cell proliferation when cultures were stimulated with anti-CD3 alone
Tfh cells provide co-stimulation as well as stimulatory cytokines to B cells leading to affinity maturation, class switch recombination (CSR) and antibody production which are all necessary for B cell responses
Summary
A crucial aspect of T-cell dependent immunity is the formation of the germinal center (GC) within the B cell follicles of secondary lymphoid organs. Naïve CD4+ T cells are localized in the T cell zone of lymphoid organs and TCR engagement with peptide/MHCII on antigen presenting cells (APC), together with the cytokines IL-21 and IL6, results in the upregulation of CXCR5 allowing these T cells to home toward the follicle [3, 4]. Normal development of Tfh cells is required for optimal formation of antibody responses primarily through the active germinal center reaction. Tfh cells promote the germinal center reaction through IL-4 and IL-21 secretion, helping B cells differentiate into GC B cells, which undergo class switch recombination (CSR) and somatic hypermutation resulting in terminal differentiation of the GC B cells into plasma cells [5, 6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
