B Lymphocytes Induce the Formation of Follicular Dendritic Cell Clusters in a Lymphotoxin α–dependent Fashion

Self Cite

B cells, but not T cells, are considered to be important for the formation of follicular dendritic cell (FDC) clusters. Stimulation with agonist mAbs against CD137 (4-1BB), a TNFR family member primarily expressed on activated T cells, was effective in promoting T cell responses, but paradoxically suppressed T-dependent humoral immunity and autoantibody production in autoimmune disease models. Our present study shows that agonistic anti-CD137 treatment activates T cells, resulting in diminished FDC networks in B cell follicles, which are important components in T-dependent humoral immune responses both before and after the initiation of an immune response. Pretreatment with anti-CD137 before the secondary immunization inhibited memory Ab responses. Interestingly, CD137 costimulation-induced diminishment of FDC is T cell dependent. In addition, both CD4+ and CD8+ T cells are recruited into FDC area and are able to regulate FDCs by CD137 costimulation through a direct or indirect mechanism. These studies have revealed a previously unappreciated role of T cells in the regulation of FDC networks.

mentioning

confidence: 64%

Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling

Sun

Blink

Chen

et al. 2005

Self Cite

“…Insufficient TNF-␣/LT␣␤ signaling by neonatal splenocytes, demonstrated to be essential for FDC migration and differentiation (36,37,40), could also account for the absence of mature FDC during early postnatal life. However, splenocytes from either 2-day-old or 1-wk-old mice were capable of rapidly inducing the differentiation of adult FDC precursors into clusters of mature FDC, as described following adoptive transfer in adult SCID recipients.…”

Section: Discussionmentioning

confidence: 99%

Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens

Pihlgren

Tougne

Bozzotti

et al. 2003

The factors limiting neonatal and infant IgG Ab responses to T-dependent Ags are only partly known. In this study, we assess how these B cell responses are influenced by the postnatal development of the spleen and lymph node microarchitecture. When BALB/c mice were immunized with alum-adsorbed tetanus toxoid at various stages of their immune development, a major functional maturation step for induction of serum IgG, Ab-secreting cells, and germinal center (GC) responses was identified between the second and the third week of life. This correlated with the development of the follicular dendritic cell (FDC) network, as mature FDC clusters only appeared at 2 wk of age. Adoptive transfer of neonatal splenocytes into adult SCID mice rapidly induced B cell follicles and FDC precursor differentiation into mature FDC, indicating effective recruitment and signaling capacity of neonatal B cells. In contrast, adoptive transfer of adult splenocytes into neonatal SCID mice induced primary B cell follicles without any differentiation of mature FDC and failed to correct limitations of tetanus toxoid-induced GC. Thus, unresponsiveness to lymphoid-mediated signals at the level of neonatal FDC precursors delays FDC maturation and GC induction, thus limiting primary Ab-secreting cell responses to T-dependent Ags in early postnatal life.

“…Then the activated/memory CD4 ϩ T cells facilitate the activation of CD8 ϩ T cells either through the production of cytokines (20,21) and/or by "conditioning" an APC (probably a DC) through T cell help, which subsequently renders the APC capable of activating CTLs via cognate interactions (7). Additionally, we cannot rule out an effect of B cells secreting cytokines or chemokines (22)(23)(24)(25); although in a milieu of many activated T cells, we doubt that they would be limiting sources of such soluble factors.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: B Cells Promote CD8+ T Cell Activation in MRL-FaslprMice Independently of MHC Class I Antigen Presentation

Chan¹,

Shlomchik

2000

Spontaneous CD8+ T cell activation in MRL-Faslpr mice is B cell dependent. It is unclear whether this B-dependent activation is mediated by direct Ag presentation via MHC class I proteins (i.e., cross-presentation) or whether activation occurs by an indirect mechanism, e.g., via effects on CD4+ cells. To determine how CD8+ T cell activation is promoted by B cells, we created mixed bone marrow chimeras where direct MHC class I Ag presentation by B cells was abrogated while other leukocyte compartments could express MHC class I. Surprisingly, despite the absence of B cell class I-restricted Ag presentation, CD8+ T cell activation was intact in the chimeric mice. Therefore, the spontaneous B cell-dependent CD8+ T cell activation that occurs in systemic autoimmunity is not due to direct presentation by B cells to CD8+ T cells.