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. 2012 Jul;20(7):1372-8.
doi: 10.1038/oby.2012.54. Epub 2012 Mar 7.

B lymphocytes in human subcutaneous adipose crown-like structures

Marie E McDonnell  1 , Lisa M Ganley-Leal, Ankeeta Mehta, Sherman J Bigornia, Melanie Mott, Qasim Rehman, Melissa G Farb, Donald T Hess, Lija Joseph, Noyan Gokce, Caroline M Apovian
Affiliations

B lymphocytes in human subcutaneous adipose crown-like structures

Marie E McDonnell et al. Obesity (Silver Spring). 2012 Jul.

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.

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Figures

Figure 1
Figure 1. CD19+ B cells in human adipose tissue
A. Forward (FSC) and side scatter (SSC) of recovered leukocytes from adipose tissue demonstrating a small cell gate, which contains lymphocytes (circled). B. Small cell gate contains a small population of CD19+ B cells. Representative of 12 tissue samples. C. CD19+ B cells express surface IgM. Gated on small cells (A). D. CD19+ B cells express TLR4. Gated on CD19+ B cells (B).
Figure 2
Figure 2. Immunohistochemistry of subcutaneous CLS
A. CD19 positive B cells are present in a CLS with CD68 positive macrophages. Nuclei are stained with hematoxylin. B. Perivascular CD19 positive B cells with nearby B cell within the tissue. C. CD19 positive control (human tonsil). D. Rare CD3 positive T cells in a CLS. E. B cell stain CD20 is negative, consistent with decreased surface levels of this marker known to occur following B cell activation.
Figure 3
Figure 3. CD19+ B cell variability in sCLS
A. A representative sCLS double stained with CD68 and CD19. A single CD19+ lymphocyte (arrow) is identified among macrophages within one section of a sCLS. (note: subject not on Metformin). Nuclei are stained with hematoxylin. B. Shown are over 10 CD19+ lymphocytes (arrows) within a one section of a sCLS. (note: subject on Metformin).
Figure 4
Figure 4. IgG and IgM immunohistochemistry of sCLS
A. Two IgG positive lymphocytes (arrow) are present within a sCLS. There is significant background staining. B. A single IgM positive lymphocyte (arrow) is present within a sCLS.
Figure 5
Figure 5. Ratio of B cells to T cells pHPF and metformin treatment
The ratio of total B:T cells quantified per HPF in and around sCLS was compared across groups based on metformin therapy. Ratios are expressed as median and range. DM+ vs. DM− indicates subjects with type 2 diabetes and without, respectively. MET+ vs. MET− indicates subject with metformin on their medication list vs. those without metformin, respectively. The * indicates a significant difference between groups, p<0.05.
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