Lasting antibody responses are mediated by a combination of newly formed and established bone marrow plasma cells drawn from clonally distinct precursors.

Current models hold that serum Ab titers are maintained chiefly by long-lived bone marrow (BM) plasma cells (PCs). In this study, we characterize the role of subpopulations of BM PCs in long-term humoral responses to T cell-dependent Ag. Surprisingly, our results indicate that 40-50% of BM PCs are recently formed cells, defined, in part, by rapid steady-state turnover kinetics and secretion of low-affinity IgM Abs. Further, for months after immunization with a hapten-protein conjugate, newly formed Ag-induced, IgM-secreting BM PCs were detected in parallel with longer-lived IgG-secreting cells, suggesting ongoing and parallel input to the BM PC pool from two distinct pools of activated B cells. Consistent with this interpretation, IgM and IgG Abs secreted by cells within distinct PC subsets exhibited distinct L chain usage. We conclude that long-term Ab responses are maintained by a dynamic BM PC pool composed of both recently formed and long-lived PCs drawn from clonally disparate precursors.

Increased alkalotolerant and thermostable ribonuclease (RNase) production from alkaliphilic Streptomyces sp. M49-1 by optimizing the growth conditions using response surface methodology.

Total of 171 alkaliphilic actinomycetes were evaluated for extracellular RNase production and Streptomyces sp. M49-1 was selected for further experiments. Fermentation optimization for RNase production was implemented in two steps using response surface methodology with central composite design. In the first step, the effect of independent fermentation variables including temperature, initial pH and process time were investigated. After identification of carbon and nitrogen sources affecting the production by one variable at a time method, concentrations of glucose and yeast extract and also inoculum size were chosen for the second central composite design. A maximum RNase activity was obtained under optimal conditions of 4.14 % glucose concentration, 4.63 % yeast extract concentration, 6.7 × 106 spores as inoculum size for 50 ml medium, 42.9 °C, 91.2 h process time and medium initial pH 9.0. Optimum activity of the enzyme is achieved at pH 11 and temperature 60 °C. The enzyme is highly stable at pH range 9.0-12.0 and at 90 °C after 2 h. Statistical optimization experiments provide 2.25 fold increases in the activity of alkalotolerant and thermostable RNase and shortened the fermentation time compared to that of unoptimized condition. The members of Streptomyces can be promising qualified RNase producer for pharmaceutical industries.