Immune and Inflammatory Responses in TNFα-deficient Mice: A Critical Requirement for TNFα in the Formation of Primary B Cell Follicles, Follicular Dendritic Cell Networks and Germinal Centers, and in the Maturation of the Humoral Immune Response

Pasparakis M., Alexopoulou L., Episkopou V., Kollias G., J.Exp.Med., 1996 Oct 1;184(4):1397-411.

Abstract: To investigate the role of TNFα in the development of in vivo immune responses we have generated TNFα-deficient mice by gene  targeting.  Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNFα is not required for normal mouse development. In the absence of TNFα mice readily succumb to L.monocytogenes infections and show reduced contact hyper- sensitivity  responses. Furthermore, TNFα knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNFa knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNFα functioning by the expression of either human or murine TNFα transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNFα in regulating the development and  organization of splenic follicular architecture  and in the maturation of the humoral immune response.

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