Partial IgA-deficiency with increased Th2-type cytokines in TGF-beta 1 knockout mice

Though it has been shown that TGF-beta 1 directs B cells to switch to IgA i n vitro, no studies have assessed TGF-beta 1 effects on mucosal vs systemic immunity in vivo. When the B cell functions of TGF-beta 1 gene-disrupted ( TGF-beta 1(-/-)) mice were analyzed, significantly decreased IgA levels and increased IgG and IgM levels in serum and external secretions were observe d. Further, analysis of Ab forming cells (AFC) isolated from both mucosal a nd systemic lymphoid tissue showed elevated IgM, IgG, and IgE, with decreas ed IBA AFC, A lack of IgA-committed B cells was seen in TGF-beta 1(-/-) mic e, especially in the gastrointestinal (GI) tract. Splenic T cells triggered via the TCR expressed elevated Th2-type cytokines and, consistent with thi s observation, a 31-fold increase in serum IgE was seen in TGF-beta 1(-/-) mice. Thus, uncontrolled B cell responses, which include elevated IgE level s, a lack of antiinflammatory IgA, and an excess of complement-binding IgG and IgM Abs, will promote inflammation at mucosal surfaces in TGF-beta 1(-/ -) mice acid likely contribute to pulmonary and GI tract lesions, ultimatel y leading to the early death of these mice.