Table 2. B1 B cell as a dominant origin of ATA μκTg+ B CLL/lymphoma.
| TC+ μκTg mice | μκTg BCR ligand | μκTg+ mature B cell | CLL/lymphoma in old aged μκTg B cell | CLL/lymphoma in old aged non-μκTg B cell |
|---|---|---|---|---|
| VH3609μ/Vk21-5κ μκTg | WT | B1 B | ++ | +/– |
| VH3609μ/Vk21-5κ μκTg | Thy-1hi | B1 B | ++ | +/– |
| VH3609μ/Vk21-5κ μκTg | Thy-1lo | MZ B > FO B | – | + B1a (endo IgM) |
| VH3609μ/Vk21-5κ μκTg | Thy-1– | FO B | – | ++ B1a (endo IgM) |
| VH3609μ/Vk21-5κ μκTg.JH– | Thy-1– | FO B | – | + B1a (IgL edited) |
| VH3609μ/Vk19-17κ μκTg | WT | MZ B and FO B | – | + B1a (endo IgM and IgL edited, including ATA B) |
VH3609μ/Vk21-5κ is ATA BCR, and VH3609μ/Vk19-17κ is AGcA BCR, both with the same IgH expression. On a WT background in TCL1+ μκTg mice, ATA B cells become mature B1 B cells and AGcA B cells become mature MZ B (and FO B) cells. CLL/lymphoma developed predominantly from ATA B1 B cells, not AGcA B cells. ATA B cells expressed by MZ B or FO B cells under Thy-1lo or Thy-1– conditions in ATA μκTg mice did not become tumors in contrast with endogenous IgM-expressing CD5+ B cells (B1a). IgL editing was permissive for the generation of B1a cells with the ability to become CLL/lymphoma, including generation of Vk21-5κ ATA B-CLL in AGcA μκTg mice.