Soluble mediators selectively repress chronically Ag-experienced B cells and differentially regulate autoreactive FO and MZ B cells. B cells (1 × 10⁵) from HEL-Ig × sHEL and HEL-Ig (A), Ars/A1 (B), or C57BL/6 mice (C) were stimulated with LPS (30 μg/mL) in the presence or absence of rsCD40L (100 ng/mL) for 4 days. Anti-HEL IgM^a (HEL-Ig and HEL-Ig × sHEL), IgM^a/κ (Ars/A1), IgM, and anti-nucleosome Ig (C57BL/6) were quantitated by ELISA. LPS-stimulated B cells (100%) secreted 9-15 μg/mL (HEL-Ig × sHEL), 16-47 μg/mL (HEL-Ig), 2-9 μg/mL (Ars/A1), 56-156 ng/mL anti-nucleosome Ig (C57BL/6), and 19-43 μg/mL IgM^b (C57BL/6) (100%) secreted. (D) 1 × 10⁵ Sm-specific (2-12H) FO and MZ B cells were sorted and stimulated with LPS (30 μg/mL) in the absence or presence of BMDCs (1 × 10⁴), BMMΦs (1 × 10⁴), rIL-6 (20 ng/mL), or rsCD40L (100 ng/mL). The number of ASCs was determined on day 3 using an Sm-specific enzyme-linked immunosorbent spot (ELISPOT). LPS-stimulated FO B cells (100%) yielded 2.8 × 10⁴ to 1 × 10⁵ spots/10⁶ cells, whereas MZ B cells (100%) yielded 2.3 × 10⁴-1.3 × 10⁵ spots/10⁶ cells. Statistical analysis was performed using 1-sample t test by comparing treated and untreated cultures. Data represent at least 3 experiments. Error bars represent plus or minus SEM. (*P ≤ .05.)