Blood clearance and tissue localization of soluble aggregates of IgG in NZB/W and NZB mice

Abstract

We studied the capacity of the mononuclear phagocytic system (MPS) of NZB/W and NZB mice to clear trace and saturating doses of soluble heat-aggregates of IgG (A-IgG) from the blood. Mature female NZB/W mice (aged 5-7 months) with early glomerulonephritis showed no differences in MPS clearance of A-IgG compared with younger NZB/W mice without glomerulonephritis. In contrast, mature NZB mice had a more rapid clearance of A-IgG and greater MPS localization of A-IgG than their younger counterparts. Further studies showed that older NZB/W mice (greater than 10 months) had a slightly more rapid clearance of A-IgG than 2-5-month-old mice (t 1/2 = 3.34 +/- 0.27 SEM vs 3.76 +/- 0.34 SEM, P less than 0.01), whereas NZB mice mice older than 10 months of age had a markedly more rapid clearance than 2-5-month-old NZB mice (t 1/2 = 2.84 +/- 0.15 SEM vs 3.76 +/- 0.32, P less than 0.005). The more rapid clearance seen in NZB mice was partly explained by greater splenic localization of A-IgG and appeared to be restricted to Fc- and/or C3b-receptor mediated clearance, in that clearance of aggregated albumin was not changed. We conclude that NZB/W mice have no impairment in MPS clearance capacity at the onset of their glomerulonephritis, and slightly increased clearance capacity late in the course of their disease. Thus, the presence of circulating immune complexes and the development of glomerulonephritis in NZB/W mice is unlikely to be due to a diminished MPS clearance capacity. NZB mice have an increase in MPS capacity to clear A-IgG as a function of age.