Studies involving administration of IL-10 protein, IL-10 gene delivery, IL-10 transgenic animals or inhibition of IL-10 activity by neutralizing mAb or gene knock-out animals suggest that the in vivo role of IL-10 in B cell function is limited.5-7 For instance, plasma immunoglobulin levels are normal in IL-10 -/- mice.8 An important exception is represented by a model of antibody-dependent autoimmunity such as systemic lupus erythematosus (SLE), in which IL-10 neutralization does affect disease onset.9
IL-10 effects on survival, proliferation and differentiation of human B cells are much more evident.7 IL-10 enhances survival of normal B cells, which correlates with increased expression of the anti-apoptotic protein bcl-2.10,11 IL-10 is also a potent cofactor for B cell proliferation:12,13 this phenomenon is further promoted by IL-2, which correlates with IL-10-induced overexpression of the high-affinity IL-2 receptor on B cells.14
Finally, B cell-derived and exogenous IL-10 promotes B cell differentiation and isotype switching.15,16 Long-term culture of B cells stimulated by either anti-CD40 or follicular dendritic cells and IL-10 results in differentiation of B cells into plasma cells, and IL-10 acts
Interleukin-10, edited by Francesco M. Marincola. ©2006 Eurekah.com.
synergistically with CD27/CD70 signals to induce plasma cell differentiation from CD27+ memory B cells.17 Accordingly, IL-10 induces IgA and IgG production by B cells of patients suffering from IgA deficiency and X-linked hyper-IgM-syndrome, respectively.18
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