MICE DEFICIENT IN NUCLEAR FACTOR (NF)-KAPPA-B P52 PRESENT WITH DEFECTS IN HUMORAL RESPONSES, GERMINAL CENTER REACTIONS, AND SPLENIC MICROARCHITECTURE/

p52 is a subunit of nuclear factor (NF)-kappa B 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 I kappa B family. To determine no nredundant physiologic roles of p52, we generated mice deficient in p5 2. Null mutant mice were impaired in their ability to generate antibod ies to T-dependent antigens, consistent with an absence of B cell foll icles and follicular dendritic cell networks in secondary lymphoid org ans, and an inability to form germinal centers. Furthermore, the splen ic marginal zone was disrupted. These phenotypes are largely overlappi ng with those observed in Bcl-3 knockout animals, but distinct from th ose of p50 knockouts, supporting the notion of a physiologically relev ant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further su that such a complex may be critical in accessory cell func tions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of t hese proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.