Figure 5. AP4 is necessary for the accumulation of somatic mutations.

(A) Frequencies of mutations in an J_H4 adjacent intronic region in Tfap4^−/− and control Tfap4^f/fcre⁻ donor GC B cells from mixed bone marrow chimeras 12 days after NP-CGG immunization. Data are pooled from three independent experiments.

(B) Frequencies of clones carrying multiple mutations in (A).

(C) Cumulative frequency distribution of V_H186.2 somatic mutations in CD45.2 donor GC B cells in (A). Data are pooled from three independent experiments.

(D and E) Expression of Aicda mRNA and frequencies of IgG₁⁺ in CD45.2 donor-derived GC B cells in (A). Data are pooled from three independent experiments.

(F) Frequencies of Igλ⁺ cells in NIP-APC-binding GC B cells from Tfap4^f/fIghg1^cre/+ and control Tfap4^+/+Ighg1^cre/+ mice ten days after NP-CGG immunization. Data are pooled from two independent experiments.

(G) NIP-APC-binding by GC B cells in (F). Data are pooled from two independent experiments. (H) NP₄-specific serum Igλ titers in Tfap4^f/fCd79a^icre/+ and control Tfap4^f/fcre⁻ mice 56 days after NP-CGG immunization. Data are pooled from two independent experiments.

(I) Frequencies of the W33L mutation in V_H186.2 BCR⁺ clones in CD45.2 GC B cells in (A). Numbers of W33L bearing clones and total number of clones sequenced are shown. Data are pooled from four independent experiments.

Data in (A, D, E, F-H) are shown by means ± SD, with unpaired Student’s t test. Kolmogorov-Smirnov test for (C). c² test with Yates correction for (I). n = 6 for each group (A-C, E-I); n = 17 for Tfap4^f/fcre⁻ and n = 14 for Tfap4^−/− (D). See also Figure S5.