AFFINITY MATURATION WITHOUT GERMINAL-CENTERS IN LYMPHOTOXIN-ALPHA-DEFICIENT MICE

AFFINITY maturation by somatic hypermutation is thought to occur withi n germinal centres(1-4). Mice deficient in lymphotoxin-alpha (LT alpha (-/-) mice) have no lymph nodes or Peyer's patches(5,6), and fail to f orm germinal centres in the spleen(7). We tested whether germinal cent res are essential for maturation of antibody responses to T-cell-depen dent antigens. LT alpha(-/-) mice immunized with low doses of (4-hydro xy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaire d production of high-affinity anti-NP IgG1. However, LT alpha(-/-) mic e immunized with high doses of NP-OVA, even though they failed to prod uce germinal centres, manifested a high-affinity anti-NP IgG1 response similar to wild-type mice. Furthermore, when LT alpha(-/-) mice were multiply immunized with high doses of NP-OVA, the predominantly expres sed anti-NP Vu gene segment VH186.2 showed somatic mutations typical o f affinity maturation(8). Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.