Mutant mice without B lymphocyte follicles

T he immune system requires the cognate interactions of T cells, B cells, and antigen-presenting cells to respond to invading antigens/pathogens. However, the peripheral lymphoid organs where immune responses occur are not simply made of a random mixture of T cells, B cells, and antigen-presenting cells. Rather they are organized into ruicroanatomic compartments that are composed mainly of T cell zones and B cell follicles. T cell zones are found in the paracortex of lymph nodes, the periarteriolar lymphoid sheaths (PALS) of spleen (Fig. 1) and the dome area of Peyer's patches. They contain both CD4 + and CD8 + T cells as well as interdigitating dendritic cells (IDC). B cell areas can be found in the form of either resting primary follicles or activated secondary follicles. A primary B cell follicle contains slgM+IgD + resting recirculating B cells and follic-ular dendritic cells (FDC) (Fig. 1). A secondary B cell follicle is composed of a follicular mantle containing slgM+IgD + resting B cells and a germinal center composed of centro-blasts, centrocytes, activated CD4 + memory T cells, CD4 + CD1 lc+CD3-germinal center dendritic cells (GCDCs) and FDC (1, 2). In addition, a third compartment, the marginal zone, observed in the spleen, contains a subset of non-recirculating slgmhighIgDl~ B cells (Fig. 1) (3, 4), marginal macrophages as well as marginal metallophils (5-7). What are the functional advantages for peripheral lymphoid tissues to be structured into complex T and B cell zones? What are the molecular mechanisms underlying the segregation of T cell zones and B cell follicles? In this issue of Tke Journal of Experimental Medicine, Pasparakis et al. report that the spleens of TNFoL knockout mice lack primary fol-licles and mature FDC (8). These mice display impaired humoral immune responses and are unable to form germi-nal centers in response to T cell-dependent antigens. This observation, together with other recent reports, highlights the fundamental role of members of the TNF-TNFR su-perfamily in the development of peripheral lymphoid organs and germinal centers. TNFo~ and LToe bind to the same receptors TNFRI (P55/CD120a) and TNFRII (P75/CD120b)(9). In addition , when one LTc~ monomer triruerizes with two identical LT[3 subunits, the heterotriruers bind a third receptor, TNFR[3 (10). In an earlier report, Chaplin's group has shown that LT-deficient mice display an abnormal splenic architecture and an inability to form germinal centers (11). However, in contrast to the TNFot-deficient mice reported herein by Pasparakis et …