Table 1.
Distribution and frequencies of dominant V186.2 mutations in B-Sharpin+/+ and B-Sharpincpdm mice immunized with NP-CGG and the ratio of mutation frequencies in B-Sharpin+/+ mice to those in B- Sharpincpdm mice.
| V186.2DJH-Cμ, CDRs | V186.2DJH-Cμ, FRs | ||||||
|---|---|---|---|---|---|---|---|
| Mutation | Frequency (x10–2 change/base) | Ratio | Mutation | Frequency (x10–2 change/base) | Ratio | ||
| /region | B-Sharpin+/+ | B-Sharpincpdm | /region | B-Sharpin+/+ | B-Sharpincpdm | ||
| AG 92C/CDR1† | 4.04 | 0.29 | 14.1 | CTT 33/FR1 | 16.8 | 17.4 | 0.97 |
| AGC 93/CDR1†* | 6.00 | 1.89 | 3.17 | GTG 36/FR1 | 6.55 | 5.86 | 1.12 |
| CAC 105/CDR1 | 3.39 | 3.73 | 0.91 | AA 38G/FR1 | 10.6 | 13.0 | 0.82 |
| AG 149G/CDR2 | 5.24 | 5.03 | 1.04 | G 46CT/FR1 | 6.41 | 6.76 | 0.95 |
| G 154AT/CDR2 | 4.85 | 4.57 | 1.06 | C 58TG/FR1 | 9.87 | 8.53 | 1.16 |
| A 160AT/CDR2 | 6.67 | 0.90 | 7.45 | CG 128A/FR2 | 8.72 | 8.72 | 1.00 |
| G 169GT/CDR2 | 5.94 | 5.24 | 1.13 | C 208TG/FR3 | 7.00 | 8.41 | 0.83 |
| AAG 177/CDR2 | 8.70 | 7.70 | 1.13 | C 223CC/FR3 | 19.3 | 19.5 | 0.99 |
| A 196GC/CDR2 | 5.36 | 6.70 | 0.80 | CAG 246/FR3 | 15.8 | 7.32 | 2.16 |
| AG 197C/CDR2 | 12.7 | 2.26 | 5.62 | TAT 285/FR3 | 25.4 | 27.8 | 0.91 |
| V186.2DJH-Cγ1, CDRs# | V186.2DJH-Cγ1, FRs# | ||||||
| Mutation | Frequency (x10–2 change/base) | Ratio | Mutation | Frequency (x10–2 change/base) | Ratio | ||
| /region | B-Sharpin+/+ | B-Sharpincpdm | /region | B-Sharpin+/+ | B-Sharpincpdm | ||
| AG 92C/CDR1† | 4.95 | 7.93 | 0.62 | GAG 30/FR1* | 11.7 | 5.36 | 2.18 |
| TG 98G/CDR1‡ | 19.7 | 4.18 | 4.71 | CTT 33/FR1* | 22.6 | 8.75 | 2.58 |
| CAC 105/CDR1 | 6.96 | 2.10 | 3.31 | AA 38G/FR1 | 17.8 | 6.96 | 2.56 |
| AG 149G/CDR2 | 3.34 | 2.46 | 1.36 | G 46CT/FR1 | 11.6 | 4.60 | 2.52 |
| G 154AT/CDR2 | 2.34 | 1.79 | 1.31 | C 58TG/FR1 | 10.4 | 5.16 | 2.02 |
| AAG 177/CDR2 | 4.96 | 2.81 | 1.77 | AAG 114/FR2 | 4.43 | 2.06 | 2.15 |
| G 184AG/CDR2 | 3.75 | 1.77 | 2.12 | CG 128A/FR2 | 10.4 | 5.43 | 1.92 |
| GAG 186/CDR2 | 3.90 | 5.11 | 0.76 | C 208TG/FR3* | 9.79 | 10.6 | 0.92 |
| A 196GC/CDR2 | 7.43 | 2.96 | 2.51 | C 223CC/FR3 | 16.6 | 16.3 | 1.02 |
| AG 197C/CDR2 | 7.87 | 12.9 | 0.61 | TAT 285/FR3* | 24.8 | 8.11 | 3.06 |
†The AG92C93 (Ser) codon has a high mutability and all mutations are replacement mutations except for AGT93 (36).
‡The TG98G (Trp) to TT98G (Leu) replacement mutation changes the affinity of Abs to NP by 10-fold (34,35). The frequency of G98 ®T98 mutation were 33.6x10–2, 11.0 x10–2, and 9.8x10–2 change/base in three B-Sharpin+/+ mice, and 7.8 x10–2, 2.9x10–2, and 0.2x10–2 change/base in three B-Sharpincpdm mice. Since only unique sequences were analyzed, the frequencies of each mutation were equivalents of the proportions of B cell clones carrying such mutations.
#The mutations depicted here had the highest frequencies in the CDRs and FRs, respectively, in B-Sharpin+/+ mice. Additional dominant mutations occurred at high frequencies in B-Sharpincpdm mice (6 in FR1, 4 in CDR2, and 3 in FR3).
*The mutations are all silent mutations.