engleski

Mice deficient in Nuclear Factor (NF)-kB/p52 Present with Defects in Humoral Mice deficient in Nuclear Factor (NF)-kB/p52 Present with Defects in Humoral Responses, Germinal Center Reactions and Splenic Microarchitecture Responses ; Germinal Center Reactions, and Splenic Microarchitecture

p52 is a subunit of nuclear factor (NF)-kB transcription factors, most closely related to p50.Previously we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the IkB family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3.Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.

NF-kB knockout mice; germinal center formation; humoral responses

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