B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

Abstract

The CXC chemokine receptor (CXCR)5 is rapidly induced on activated CD4 + T cells, allowing migration toward secondary lymphoid tissue follicles, where the CXCR5 ligand CXCL13/ BCA-1 is produced. Such CXCR5 + T cells provide efficient help for B cell immunoglobulin production and are termed follicular B helper T (T FH ) cells. However, the molecular mechanisms by which T FH cells provide B cell help are unknown. Here, we demonstrate that newly generated (antigen-primed) T FH cells express a phenotype consistent with induction of B cell proliferation, but co-culture with primed B cells resulted in a switch to a plasma cell-inducing phenotype, characterized by loss of CD154, induction of CD70 and an increase in IL-10 production capacity. The ability to produce IL-10 could be maintained as a stable phenotype, but its secretion was strictly dependent on inducible costimulator (ICOS) signaling. Furthermore, B cells preserved a lymph node migration phenotype in proliferating T FH cells by preventing the loss of CC chemokine receptor (CCR)7 and the induction of CCR5. Thus, B cells directly modulate the B cell helper phenotype in T FH cells and actively promote their prolonged co-localization with these cells.

Regulation of late B cell differentiation by intrinsic IKKα-dependent signals

“…ϩ follicular T H (T FH ) cells (35) and are consistent with the observation that interaction with B cells affects the differentiation of T FH cells ex vivo (36). However, MT/AA chimeras were not completely devoid of ICOS ϩ CD4 ϩ cells (Fig.…”

Modelling Two Possible Mechanisms for the Regulation of the Germinal Center Dynamics

“…This hypothesis is supported by experimental evidence that show a change in the FDC phenotype during a GC reaction (5) and by the fact that T cells play different roles in different phases of the GC (20,21). Under this hypothesis, we propose two submodels corresponding to B cell proliferation 1.0 0.5 n 10.0 10.0 a p, maximum effective rate of B cell proliferation; k, maximum rate of B cell selection, , day by which half of the FDC/T cells are differentiated, p B , proliferation rate of centroblasts; k B , rate of centroblast differentiation into centrocytes; k C , rate of centrocyte selection; n, number of centroblast divisions.…”

“…Interactions of centrocytes with FDCs and T cells provide survival signals to the centrocytes and possibly induce the differentiation to a distinct effector stage of FDCs (5) and T cells (20,21). We propose that the interaction of centrocytes with differentiated cells promotes their differentiation into AFCs or memory B cells that leave the GC, ultimately terminating the reaction.…”

“…Furthermore, it has been reported that FDCs change their phenotype during the GC reaction (5) and that B cell interaction with both FDCs and T cells provides survival signals to B cells and may induce FDC and T cell differentiation. Although for GC T cells there is still not much information, it is known that T cells are essential for early processes in the GC, such as triggering the hypermutation on B cells, and for different later processes, such as the differentiation of B cells into memory and plasma cells; this suggests that GC T cells may also change their effector state (20,21).…”

Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy

“…One scenario is that during B cell repopulation, stochastic events and environmental hits fail to converge and reproduce the breakdown of tolerance characteristic of the initial disease. Alternatively, the absence of B cells could create profound changes in other immune cells, including T cell subsets (altered T helper cell polarization, defective migration of CXCR5ϩ follicular T helper cells, or T regulatory cell expansion) (7,8,(38)(39)(40) and DCs (9), as has been suggested in recent studies (41,42). Finally, a reconstitution dominated by immature and virgin B cells may lead preferentially to T cell anergy (10).…”