High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences. We developed a five B cell-associated gene signature for prognosis of high grade glioma patients, which is independent of clinicopathological and genetic features. The signature identified high risk patients suitable for chemoradiotherapy, whereas low risk patients should rule out chemotherapy with radiotherapy only. We found that tumors of TCGA Mesenchymal subtype and wild type IDH1 were preferentially stratified to the high risk group, which bore strong immunosuppressive microenvironment, while tumors of TCGA Proneural subtype and mutated IDH1 were significantly accumulated to the low risk group, which exhibited less immunosuppressive state. The five B cell-associated gene signature predicts poor survival of high risk patients bearing strong immunosuppression and helps select optimal therapeutic regimens for glioma patients.