TACI and BAFF-R mediate isotype switching in B cells

Abstract

The tumor necrosis factor family members BAFF and APRIL induce Ig isotype switching in human B cells. We analyzed the ability of BAFF and APRIL to induce isotype switching in murine B cells to IgG1, IgA, and IgE. APRIL and BAFF each engage two receptors, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), on B cells. In addition, BAFF engages a third receptor on B cells, BAFF-R. To determine the role of these receptors in isotype switching, we examined B cells from mice deficient in TACI, BCMA, and BAFF-R. The results obtained indicate that both TACI and BAFF-R are able to transduce signals that result in isotype switching.

Figure 1.

Induction of CSR by BAFF and APRIL in negatively sorted B cells from CD40 ^{− / −} mice. (A) IgG1, IgA, and IgE synthesis in negatively sorted B cells. Results represent mean and SD of at least three experiments. (B) Surface expression of IgG1 in negatively sorted B cells. Numbers represent the percentage of sIgG1⁺ cells. (C) Semiquantitative RT-PCR analysis of the expression of γ1, α, and ɛGLT, Iμ-Cγ1, Iμ-Cα, Iμ-Cɛ, and AID transcripts. (D) Sμ→Sɛ, Sμ→Sα, and Sμ→Sγ1 deletional switch recombination measured by DC-PCR. Dividing lines are used to group different dilutions (1:1, 1:3, and 1:9) of cDNA from B cells cultured in the same experiment with various stimuli. All samples were loaded contiguously in the same gel, except for cDNAs from cells stimulated with LPS + IL-4 and LPS + TGFβ which were loaded in noncontiguous lanes of the gel. Results in B, C, and D are representative of three experiments.

Figure 2.

Role of TACI and BCMA in inducing IgG1, IgA, and IgE synthesis. Negatively sorted B cells from WT, TACI^−/−, and BCMA^−/− mice were stimulated with (A) APRIL, (B) BAFF, and (C) αCD40 and LPS as controls. Results represent mean and SD of three experiments.

Figure 3.

Molecular events involved in IgG1, IgA, and IgE switching in negatively sorted B cells from WT, TACI ^−/−, and BCMA ^−/− mice. Dividing lines are used to demarcate noncontiguous parts of the same gel Results are representative of three experiments.