From the Guidelines
T follicular helper (Tfh) cells play a crucial role in the development and function of germinal center (GC) B cells, providing essential signals for their proliferation, survival, and differentiation into plasma cells and memory B cells. The interaction between Tfh cells and GC B cells is a complex process, involving direct cell-to-cell contact and cytokine secretion, primarily occurring in secondary lymphoid organs 1. Tfh cells express CXCR5, allowing them to migrate to B cell follicles, and secrete IL-21, which promotes B cell proliferation, survival, and differentiation into plasma cells and memory B cells.
Some key points about the interaction between Tfh cells and GC B cells include:
- Tfh cells express CD40L, which binds to CD40 on B cells, delivering survival signals and promoting class-switch recombination 1
- They produce cytokines like IL-4 and IFN-γ that direct antibody isotype switching
- Through the process of affinity maturation, Tfh cells selectively help B cells with high-affinity receptors by providing survival signals, while those with lower affinity undergo apoptosis
- Dysregulation of Tfh cells can lead to autoimmune disorders or immunodeficiencies, highlighting their importance in balanced immune responses
The study by 1 provides insight into the mechanism of Tfh cell interaction with GC B cells, and how disease-modifying antirheumatic drugs (DMARDs) can impact this process. For example, low-dose methotrexate (MTX) can impact the expression of cytokines, B cell, and CD8+ T cell responses, while mycophenolate mofetil can also affect this interaction. Overall, the evidence suggests that Tfh cells are essential for the development and function of GC B cells, and their dysregulation can have significant consequences for the immune response.
From the Research
Impact of T Follicular Helper Cells on GC B Cells
- T follicular helper (TFH) cells play a crucial role in the germinal center (GC) reaction, where they provide help to B cells and facilitate their selection and differentiation 2.
- The interaction between TFH cells and GC B cells is critical for the generation of high-affinity antibodies and long-term humoral immunity 2, 3.
- TFH cells continually emigrate into the follicle and neighboring GCs, ensuring maximal diversification of T cell help and accommodating antigenic variation during the immune response 3.
- The dynamic exchange of TFH cells between GCs allows for the selection of high-affinity B cells and their clonal expansion 3, 4.
- TFH cells form large but transient contacts with GC B cells, eliciting transient and sustained increases in TFH intracellular free calcium (Ca(2+)) and inducing selection through repeated transient elevations in intracellular Ca(2+) 4.
Regulation of GC B Cells by T Follicular Helper Cells
- TFH cells regulate GC B cell selection and differentiation through the expression of cytokines such as interleukin-4 and -21 4.
- The balance between TFH cells and T follicular regulatory cells (Tfr) is critical for maintaining GC homeostasis and preventing antibody-mediated autoimmunity 5.
- Tfr cells regulate GC responses by suppressing excessive TFH cell activity and maintaining tolerance towards self 5.
- The development and biology of TFH cells, including their metabolic regulation, are essential for understanding GC responses and the generation of high-affinity antibodies 5.