K10−/−, Anti-K10 depletion, or Bim−/− prevent ischemia. 24h before antibody injections, one ear of each mouse was exposed to 4°C for one minute. Ear lengths were measured at baseline and Day 14. A. Anti-K10 MAb (50 μg) injected via tail vein (n = 5). In K10−/−, no ear loss was observed, regardless of cold exposure. BALB/C mice had ear loss after cold exposure in 4/5 mice (*change in ear length versus K10−/− mice T Test p = 0.008). B. Anti-K10+ human Raynaud’s serum depletion by incubation with his6-K10-loaded nickel-Sepharose beads yielded control serum levels of anti-K10 ELISA reactivity. Nickel-Sepharose mock depletion had minimal effect. C. In B6 mice, ear tissue was lost in 5/5 recipients of mock-depleted serum, each worse on the cold-exposed side, but in 0/5 recipients of anti-K10 depleted serum (*Fisher’s Exact p = 0.008). D. Bim−/− and germline control B6 mice (n = 10) received 50 μl anti-K10+ human serum; only cold-exposed ears shown. Squares: ear loss observed; Circles: no ear loss. Bim−/− mice were protected from ear loss versus Bim-intact mice (*Fisher’s Exact p = 0.033).