Table 1.
Contribution of different cytokines to the in vitro behavior of human B cells.
| Cytokine | Effect on B cells | Reference |
|---|---|---|
| CD40L | Induces activation, blastogenesis, proliferation | (25 ) |
| IL-2 | Enhances proliferation of CD40L-stimulated B cells | (25, 26, 30, 36, 38, 39, 44, 104, 144, 145 ) |
| Co-operates with other cytokines/stimulatory factors to enhance differentiation of activated B cells | ||
| IL-4 | Enhances proliferation induced by CD40L, BCR engagement | (25, 33, 37, 40, 45 ) |
| Induces expression of AICDA | ||
| Induces CSR, preferentially to IgG1, IgG4, and IgE | ||
| IL-6 | Promotes survival and function of in vitro-derived as well as primary and malignant plasma cells | (32, 44 –47 ) |
| IL-10 | Enhances proliferation induced by CD40L, BCR engagement | (25, 26, 31, 34, 42, 59, 60, 144 ) |
| Induces expression of AICDA, BLIMP-1 | ||
| Induces CSR, preferentially to IgG1, IgG3 | ||
| Co-operates with TGF-β to induce CSR to IgA | ||
| Promotes differentiation of B cells to become plasma cells secreting IgM, IgG, IgA | ||
| IL-12 | Induces B cells to differentiate into IgM-secreting cells | (32, 54 ) |
| Co-operates with IL-6 to augment IgM secretion | ||
| Suppresses IL-4-induced IgE production | ||
| IL-13 | Enhances proliferation induced by CD40L, BCR engagement | (28, 29, 41, 50 ) |
| Induces expression of AICDA | ||
| Induces CSR, preferentially to IgG1, IgG4, and IgE | ||
| Effects essentially overlap with those of IL-4 | ||
| IL-15 | Enhances proliferation of B cells stimulated with CD40L or BCR engagement | (24 ) |
| Induces secretion of IgM, IgG1, and IgA by CD40L-stimulated B cells | ||
| Magnitude of the effect was comparable to IL-2 | ||
| IL-21 | Currently, the most potent cytokine identified capable of regulating human B-cell function | (60, 71, 76, 83, 84, 96 –101, 103, 106, 107, 121 ) |
| Enhances proliferation induced by CD40L, BCR engagement | ||
| Induces expression of AICDA, BCL-6, BLIMP-1, XBP-1 | ||
| Induces CSR, preferentially to IgG1, IgG3, and IgA1 | ||
| Promotes differentiation of B cells to become plasma cells secreting IgM, IgG, IgA, and IgE | ||
| Synergizes with IL-4 for CSR to IgG and secretion of IgE | ||
| Sustain survival of primary plasma cells present in secondary lymphoid organs | ||
| Growth and survival factor for malignant plasma cells (i.e., myeloma) | ||
| Requires functional STAT3 to induce plasma cells differentiation | ||
| IFNα, IFNγ | Inhibits CD40L-induced B-cell proliferation | (25, 33, 36, 40 ) |
| Inhibits IL-4 induced IgE secretion | ||
| IFNα primes activated B cells to differentiate into precursors of plasmablasts, that become plasmablasts in response to IL-6 | ||
| TNFα | Membrane TNFα expressed by CD4+ T cells acts as a co-stimulus to promote B-cell differentiation induced by CD40L and IL-4 | (27, 33, 63) |
| BAFF/APRIL | BAFF promotes survival of transitional B cells, as well as of early plasma cells and some malignant plasma cells | (64 –66 ) |
| BAFF and TACI can induce CSR to various isotypes, and can induce secretion of these Ig’s when combined with BCR signaling and cytokines (e.g., IL-4, IL-10, IL-15) | ||
| TGFβ | Inhibits IL-4 induced IgE secretion | (31, 33 ) |
| Can induce CSR to IgA, in combination with IL-10 |
CSR, class switch recombination.