In vivo blockade of LTβR by soluble LTβR-Ig disrupts ATLO structure, reduces Cxcl13 and Glycam1 mRNAs, and attenuates serum CXCL13 levels. ApoE ^−/− mice at 75 wk were treated three times with 75 µg LTβR-Ig (n = 11) or the same concentration of human IgG (n = 6) i.p. every 7 d for 3 consecutive weeks. (a) At the end of the treatment period, LTβR-Ig treatment was monitored in the spleen by loss of integrity of marginal zones (MAdCAM-1), FDCs (CD35), cell proliferation (Ki67), centrocytes (PNA), and follicular mantle B cells (IgD); note loss of FDCs and centrocytes and that mantle IgD⁺ B cells are less affected. (b) ATLO stages were determined after staining with CD3ε (T cells), B220 (B cells), and CD35 antisera (FDC). χ² test, P < 0.05. (c) HEVs (PNAd⁺) abundance was determined by the χ² test in LTβR-Ig versus control IgG-treated mice (P < 0.05); representative stainings are shown at left. (d) Aortae of LTβR-Ig– (n = 6) or control IgG-treated (n = 3) mice were examined by qRT-PCR for Cxcl13 (P < 0.01), Glycam1 (P < 0.05), and Il7r (P < 0.05) mRNAs; unpaired Student's t test; means ± SEM. (e) serum CXCL13 levels of control hu-IgG–treated mice (n = 4) or LTβR-Ig–treated mice (n = 7). Means ± SEM (P < 0.01). Bars, 100 µm.