miR-142 KO mice are immunodeficient. (A-C) Defective humoral immune responses in miR-142−/− mice. (A) Analysis of anti-TNP antibody production (IgM, left; IgG1, right) in 8-week-old female WT (n = 6) and KO (n = 6) mice challenged with T-cell–dependent antigen (TNP-KLH, 100 μg in complete Freund adjuvant) by serum Ig ELISA. Peripheral blood was collected 7, 14, and 21 days postimmunization. (B) Immunohistochemical analysis of GC formation in spleen sections from WT (top) and KO (bottom) mice challenged with TNP-KLH. Spleens were collected 21 days postimmunization and stained with PNA (brown stain). Note normal GC formation (marked by arrows) in WT spleen, whereas KO tissue lacks GCs and instead displays multiple PNA+ myeloid cell clusters (marked by arrows). (C) Analysis of anti-TNP antibody production (IgM, left; IgG3, right) in 6-week-old female WT (n = 6) and KO (n = 4) mice challenged with TI antigen (TNP-Ficoll, 100 μg in phosphate-buffered saline) by serum Ig ELISA. Peripheral blood was collected 7, 14 and 21 days post immunization. (D) miR-142−/− mice are highly susceptible to infection with HSV-1 virus. Kaplan-Meier survival curves of WT (n = 6) and KO (n = 6) mice upon infection with either low (3200 plaque-forming units) or high (105 plaque-forming units) dose of HSV-1 virus. P values for the comparison of WT and KO curves were identical for both HSV-1 doses and were calculated using a log-rank (Mantel-Cox) test. Results are shown as means ± SD. P values were calculated using Student t test. *P ≤ .05; **P ≤ .01; ***P ≤ .001; ****P ≤ .0001. Ag, antigen; ND, not detected.