Affinity maturation without germinal centres in lymphotoxin-alpha-deficient mice.
Matsumoto, Mitsuru; Lo, Stanley F.; Carruthers Cynthia J. L.; Min, Jingjuan; Mariathasan, Sanjeev; Huang, Guangming; Plas, David R.; Martin, Steven M.; Geha, Raif S.; Nahm, Moon H.; Chaplin, David D.
[Letter] Nature. 382(6590):462-466, August 1, 1996.

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AFFINITY maturation by somatic hypermutation is thought to occur within germinal centres *RF 1-4*. Mice deficient in lymphotoxin-alpha (LT alpha sup -/- mice) have no lymph nodes or Peyer's patches [5,6], and fail to form germinal centres in the spleen [7]. We tested whether germinal centres are essential for maturation of antibody responses to T-cell-dependent antigens. LT alpha sup -/- mice immunized with low doses of (4-hydroxy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaired production of high-affinity anti-NP IgG1. However, LT alpha sup -/- mice immunized with high doses of NP-OVA, even though they failed to produce germinal centres, manifested a high-affinity anti-NP IgG1 response similar to wild-type mice. Furthermore, when LT alpha sup -/- mice were multiply immunized with high doses of NP-OVA, the predominantly expressed anti-NP V H gene segment V H186.2 showed somatic mutations typical of affinity maturation [8]. Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.

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