Local IgA and IgM Rheumatoid Factor Production in Autoimmune MRL/Ipr Mice

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Abstract
Spontaneous local immunoglobulin (IgA, IgG, IgM) as well as IgA and IgM rheumatoid factor (RF) production in salivary glands, lymph nodes, and spleen was analyzed at various ages in autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice by using an ELISPOT assay. The longitudinal design of the study permitted correlations with severity of disease in salivary glands (sialadenitis). Local production of immunoglobulins in salivary glands and lymph nodes occurred with a pattern of IgG«lgM>IgA. This isotype pattern differed from that simultaneously observed in spleen where IgG did not predominate to the same extent. Moreover, the spleen was the major site of IgM production. Rheumatoid factors constituted a significant fraction of local IgA and IgM in involved salivary glands. The pattern of IgA RF isotype expression in salivary glands contrasted with that observed in spleen. While the number of IgA and IgG secreting cells increase at an early age, the peak of RF production in salivary glands occurs in older mice. Furthermore, the level of immunoglobulin secretion was positively correlated with disease severity in salivary glands. The results suggest that local RF production is a secondary event in salivary gland inflammation in MRL/lpr mice rather than an initiating factor in this process.