Human follicular helper T lymphocytes critical players in antibody responses

Abstract

Follicular helper T lymphocytes are a subpopulation of CD4 + T lymphocytes initially identified in germinal centers of follicles found in secondary lymphoid organs. The primary function of follicular helper T lymphocytes is to help B lymphocytes’ antibody production. Changing of antibody class and affinity, B cell differentiation and memory generation depend on cooperation between follicular helper T lymphocytes and B cells. In blood, follicular helper T lymphocytes are called circulating follicular helper T lymphocytes. They are considered to have specificities similar to those developed in the secondary lymphoid organs. The phenotype of human follicular helper T lymphocytes is given by simultaneous expression of the markers CXCR5, Bcl-6, CD40L, PD-1, and ICOS. In germinal centers, follicular helper T lymphocytes synthesize interleukin 21 as predominant cytokine. In blood, subpopulations of circulating follicular helper T lymphocytes can be recognized, with different expressions of the classical follicular helper T lymphocytes markers and, in addition, can express other markers such as CXCR3 and CCR6. Presently, there is great interest in follicular helper T lymphocytes and circulating follicular helper T lymphocytes in vaccination studies as indicators of immunization efficacy. In addition, follicular helper T lymphocytes are investigated as possible markers of activity in many diseases and potential therapeutic intervention. This short review describes aspects of immunobiology and quantification of follicular helper T lymphocytes and circulating follicular helper T lymphocytes, and presents a few examples of related findings in systemic lupus erythematosus, rheumatoid arthritis, HIV infection and vaccination.

Impairment of CD4+ T and Memory B Cell Responses but Normal Memory CD8+T-Cell Activation on Crohn’s Disease after COVID-19 Vaccination: A Twin Case

“…Nevertheless, Salinas et al (2011) suggested that anti-TNF therapy could induce an impairment of memory B cells after hepatitis B and Streptococcus pneumoniae vaccination through T-cell dependent humoral responses [18]. It is worthy to note that circulating CD4+ helper T cells are important to activate the follicular CD4+ helper T cells, which are crucial for induction of antibody production by B cells in the germinal center for affinity maturation and humoral memory response even after vaccination or viral infections [19,20]. Here, it was observed that Infliximab therapy regulated the Crohn's disease, as twin 2 did not present any signal or symptoms of gut inflammation during COVID-19 vaccination, and the presence of Infliximab may have a role in the reduction/delayed of central memory CD4+ T cells, CD4+ Th1, and Th2 responses, as well as in the absence of specific IgG antibody production and memory B cell activation compared to the healthy twin (twin 1).…”

The CXCL13/CXCR5 Immune Axis in Health and Disease—Implications for Intrathecal B Cell Activities in Neuroinflammation

“…With blood easily available compared to tissues, investigating cTfh cells and their activation states, frequencies, clonal expansions, and circulating memories quickly emerged as surrogate markers for the GC activity of lymphoid tissues [ 70 ] and for monitoring adaptive immune responses to infection and vaccination, including HIV, influenza, and SARS-CoV-2 [ 23 , 24 , 25 , 56 , 66 , 71 , 72 ].…”