Lymphotoxin and TNF Produced by B Cells Are Dispensable for Maintenance of the Follicle-Associated Epithelium but Are Required for Development of Lymphoid Follicles in the Peyer’s Patches

Tumanov, Alexei V.; Kuprash, Dmitry V.; Mach, Julie A.; Nedospasov, Sergei A.; Chervonsky, Alexander V.

doi:10.4049/jimmunol.173.1.86

Cited by 57 publications

(51 citation statements)

References 36 publications

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“…M cells in the PP have been implicated in the mechanism of murine listeriosis [32], although this issue remains controversial [33]. Since conventional TNF-KO mice develop normal M cells in their PP [30] while TNF D/D mice lack PP altogether, our results clearly establish that PP in TNF -/-mice per se play no obligatory role in pathogenesis or protection of mice from intestinal Listeria infection.…”

Section: Since Tnfsupporting

confidence: 52%

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Novel tumor necrosis factor‐knockout mice that lack Peyer's patches

et al. 2005

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We generated a novel tumor necrosis factor (TNF) null mutation using Cre-loxP technology. Mice homozygous for this mutation differ from their "conventional" counterparts; in particular, they completely lack Peyer's patches (PP) but retain all lymph nodes. Our analysis of these novel TNF-knockout mice supports the previously disputed notion of the involvement of TNF-TNFR1 signaling in PP organogenesis. Availability of TNF-knockout strains both with and without PP enables more definitive studies concerning the roles of TNF and PP in various immune functions and disease conditions. Here, we report that systemic ablation of TNF, but not the presence of PP per se, is critical for protection against intestinal Listeria infection in mice.

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Section: Since Tnfsupporting

confidence: 52%

“…4). Nevertheless, PP in TNF -/-mice showed normal development of follicle-associated epithelium and normal distribution of M cells, suggesting that these PP are at least partially functional [29,30].…”

Section: Since Tnfmentioning

confidence: 99%

Novel tumor necrosis factor‐knockout mice that lack Peyer's patches

et al. 2005

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“…In contrast to MLNs, the organization of PPs was predominantly regulated by B cell-derived TNF (supplemental Figure 6), consistent with a previous study. 29 PP from B-TNF KO mice lacked FDCs and organized B-cell follicles (supplemental Figure 6). TNF produced by T cells did not play any appreciable role in organization of PPs since T-TNF KO mice displayed normal PP microarchitecture (supplemental Figure 6), and T,B-TNF KO mice did not show additional defects in PP structure, compared with B-TNF KO mice (supplemental Figure 6).…”

Section: Organization Of Lns Is Dependent On Cooperation Between Tnf-mentioning

confidence: 99%

Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs

Tumanov

Grivennikov

Kruglov

et al. 2010

Blood

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IntroductionSecondary lymphoid organs provide an important microenvironment for the initiation and development of efficient immune responses. Their highly sophisticated structure allows migration and interactions between antigen-presenting cells, T and B lymphocytes, as well as follicular dendritic cells (FDCs) and other stromal cells. The cooperation of the lymphoid cells within secondary lymphoid organs dramatically increases the probability of interactions of rare B, T, and antigen-presenting cells that result in effective generation of humoral immune responses (reviewed in Fu and Chaplin, 1 Mebius, 2 and Allen et al 3 ).Tumor necrosis factor (TNF) and lymphotoxin (LT) are cytokines required for both formation and maintenance of the microarchitecture of the secondary lymphoid organs, acting primarily through their receptors TNFRp55 and LT␤R, respectively, and engaging classical and alternative nuclear factor-B (NF-B) pathways. 1,4,5 In vivo TNF is produced by many cell types, including lymphoid and stromal cells, and can exist in membranebound as well as in soluble forms. 6 Systemic TNF ablation in mice results in the impairment of humoral immune responses, host defense functions, and in multiple defects in lymphoid tissues including disruption of primary B-cell follicles and absence of germinal centers (GCs) and FDCs. [6][7][8][9][10] FDCs are key components in the dynamic organization of the germinal center structure and are essential for generation of efficient immune responses as well as for support of follicular microarchitecture and migration of B cells to the follicles. 3,[11][12][13] Accordingly, mice that lack FDCs show reduced specific immunoglobulin G (IgG) antibody responses to T-cell-dependent antigens. 1,5 Several studies addressed TNF-and LT-dependent mechanisms that may regulate the generation of FDCs and B-cell follicles in different secondary lymphoid organs. 14,15 In particular, in contrast to the spleen, the generation of FDCs in lymph nodes (LNs) and PP is independent of surface LT expression by B and T cells. 4,15 While the critical role of B-cell-derived TNF and LT for development of FDCs and B-cell follicles in spleen has been well established, 1,16,17 the contribution of various TNF-producing cells in organization of secondary lymphoid organs other than spleen remains unknown.To define the role of TNF produced by specific cell types in development and maintenance of secondary lymphoid organs, we used mice with conditional inactivation of TNF gene restricted to either B cells (B-TNF knockout [KO]) or T cells (T-TNF KO) or to both T cells plus B cells (T,B-TNF KO). Some of these mice were also crossed to mutant mice expressing only membrane-bound TNF 18 to distinguish between 2 molecular forms of TNF produced by a given cellular source. Our results obtained using this experimental panel unravels distinct contributions of TNF signals originating from B and T cells to the maintenance of distinct lymphoid tissues, such as spleen, LNs, and Peyer patches (PPs), and to the efficiency of humor...

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“…[4][5][6][7] Accumulating evidence has indicated that the interactive processes involving chemokines and cytokines of the tumor necrosis factor superfamily (lymphotoxins/tumor necrosis factor [TNF]) play a critical role in the orientation of the splenic microarchitecture, such as compartmentalization of T and B cells, formation of marginal zone (MZ), and development of reticular morphology known as the FDC network in secondary lymphoid organs. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] Ablation of such signals in adult animals leads to the reduction, although not the complete eradication, of immune response characterized by reduced isotype switching, delayed affinity maturation, and compromised B-cell memory. 22 Therefore, the proper formation of microarchitecture within secondary lymphoid organs, including the FDC network, is essential for efficient and/or rapid immune response.…”

Section: Introductionmentioning

confidence: 99%