Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of human respiratory syncytial virus infection

BACKGROUND AND AIMS: Production of antibody in the lungs is an essential defense mechanism against respiratory pathogens. However, little is known about the mechanisms of local B cell activation in airway mucosa. Previously, we have demonstrated expression of the B cell differentiation factor, BAFF in human RSV infection (McNamara et al 2013 Thorax). To better understand this process we examined BAFF expression in a murine model of RSV infection and measured expression of the chemokines CXCL13, CCl19 and CCl21 which could influence lymphocyte recruitment. METHODS: We measured BAFF, CXCL13, CCL19 and CCL21 expression in homogenised lung tissue from control mice at day 0 and mice challenged with RSV (A2 strain) or control UV-treated RSV at days 1,2,4 or 7 post infection (n=3) by ELISA. Cytokine mRNA and RSV N gene expression were measured by Taqman PCR. RESULTS: BAFF was elevated significantly post RSV infection at day1 (mean1092pg/ml, P=0.07), day2 (1157pg/ml, P=0.01) and day 7(2941 pg/ml, P=0.0001) in comparison to UV treated RSV control on day1 (421pg/ml), day2 (370 pg/ml) and day7 (393pg/ml). BAFF mRNA expression was similarly increased on day 1 (fold increase 2, P=0.03) and day 7(1.7, P=0.02). CXCL13 protein was increased post RSV infection at day 1 (mean762pg/ml, P=0.01), day2 (612pg/ml, P=0.02), and day 7 (388pg/ml, P=0.007) in comparison to control day 1 (374pg/ml), day2 (278pg/ml) and day7 (249pg/ml). CCL19 or CCL21 levels were not increased. CONCLUSION: RSV infection results in up-regulated BAFF and CXCl13 expression, consistent with a role for CXCL13 in recruiting B cells and BAFF in promoting airway B cell differentiation.