title: B lymphocytes in human subcutaneous adipose crown-like structures.
abstract: Accumulation of macrophages and T cells within crown-like structures (CLS) in subcutaneous adipose tissue predicts disease severity in obesity-related insulin resistance (OIR). Although rodent data suggest the B cell is an important feature of these lesions, B cells have not been described within the human CLS. In order to identify B cells in the human subcutaneous CLS (sCLS) in obese subjects and determine whether the presence of B cells predict insulin resistance, we examined archived samples of subcutaneous and omental fat from 32 obese men and women and related findings to clinical parameters. Using immunohistochemistry, we identified B (CD19(+)) and T cells (CD3 (+)) within the sCLS and perivascular space. The presence and density of B cells (B cells per high-power field (pHPF), T cells pHPF, and B cell:T cell (B:T) ratio) were compared with measures of insulin resistance (homeostasis model assessment (HOMA)) and other variables. In 16 of 32 subjects (50%) CD19(+) B cells were localized within sCLS and were relatively more numerous than T cells. HOMA was not different between subjects with CD19(+) vs. CD19(-) sCLS (5.5 vs. 5.3, P = 0.88). After controlling for diabetes and glycemia (hemoglobin A(1c) (HbA(1c))), the B:T ratio correlated with current metformin treatment (r = 0.89, P = 0.001). These results indicate that in human OIR, B cells are an integral component of organized inflammation in subcutaneous fat, and defining their role will lead to a better understanding of OIR pathogenesis and potentially impact treatment.
authors.affiliation: Department of Medicine and Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University School of Medicine, Boston, MA, USA. marie.mcdonnell@bmc.org
authors.forename: Marie E
authors.initials: ME
authors.lastname: McDonnell
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ganley-Leal
authors.forename: Ankeeta
authors.initials: A
authors.lastname: Mehta
authors.forename: Sherman J
authors.initials: SJ
authors.lastname: Bigornia
authors.forename: Melanie
authors.initials: M
authors.lastname: Mott
authors.forename: Qasim
authors.initials: Q
authors.lastname: Rehman
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Farb
authors.forename: Donald T
authors.initials: DT
authors.lastname: Hess
authors.forename: Lija
authors.initials: L
authors.lastname: Joseph
authors.forename: Noyan
authors.initials: N
authors.lastname: Gokce
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Apovian
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000276:immunology / Q000473:pathology*; D009852:Omentum / Q000276:immunology / Q000473:pathology*; D011237:Predictive Value of Tests; D050151:Subcutaneous Fat / Q000473:pathology*
chemical_list: D018941:Antigens, CD19; D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human