Affinity maturation without germinal centres in lymphotoxin-α-deficient mice

Abstract

AFFINITY maturation by somatic hypermutation is thought to occur within germinal centres^1–4. Mice deficient in lymphotoxin-α (LTα^−/− mice) have no lymph nodes or Peyer's patches^5,6, and fail to form germinal centres in the spleen⁷. We tested whether germinal centres are essential for maturation of antibody responses to T-cell-dependent antigens. LTα^−/− mice immunized with low doses of (4-hydroxy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaired production of high-affinity anti-NP IgGl. However, LTα^−/− mice immunized with high doses of NP-OVA, even though they failed to produce germinal centres, manifested a high-affinity anti-NP IgGl response similar to wild-type mice. Furthermore, when LTα^−/− mice were multiply immunized with high doses of NP-OVA, the predominantly expressed anti-NP VH gene segment VH186.2 showed somatic mutations typical of affinity maturation⁸. Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.