Abstract
Over the past 25 years it has become clear that B and T lymphocytes go through a range of interactions and migratory events when B cells differentiate to become high-affinity, antibody-secreting cells. This B-cell differentiation is associated with multiple sequential cognate interactions. In this issue of the European Journal of Immunology, Turqueti-Neves et al. [Eur. J. Immunol. 2014. 44: 2130–2138] show that IL-4, a cytokine well known as a regulator of Ig class switch recombination, has another as-yet-unappreciated role. The authors show that IL-4 produced by T-helper cells outside germinal centers has a major effect on the early stages of germinal-center B-cell differentiation. This Commentary will summarize their findings and relate them to what we know on the sequence of cognate interactions and migratory events B cells undergo during T-dependent immune responses.
Highlights
On top of this involved series of events, B cells repeatedly interact with T cells, while the T cells themselves differentiate alongside B cells
After cognate interaction between B cells and T cells, CCR7 ligand sensitivity is lost and B cells and T cells move back toward the outer boundaries of the follicles, a migration that is driven by a loss of CCR7 and prevailing signaling of EBVinduced molecule 2 (Ebi2) [6, 13]
Signals critical for GC development are exchanged in these sites [15]. It is only after the loss of Ebi2 expression [6, 16], and the induction of S1P2 [17], that B cells assemble at the centre of the follicles to form GCs, the sites where hypermutation, affinity maturation, and further cognate interactions between B cells and T cells [18] take place (Fig. 1)
Summary
It is at the follicle — T-zone interphase that primed T cells can provide signals for cognate B-cell stimulation for the first time, that is CD40L [11] and/or T-cell cytokines that induce Ig class switch recombination [12]. It is only after the loss of Ebi2 expression [6, 16], and the induction of S1P2 [17], that B cells assemble at the centre of the follicles to form GCs, the sites where hypermutation, affinity maturation, and further cognate interactions between B cells and T cells [18] take place (Fig. 1).
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