Comprehensive Physiology Wiley Online Library

The Role of B Lymphocyte Subsets in Adipose Tissue Development, Metabolism, and Aging

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Abstract

Adipose tissue contains resident B lymphocytes (B cells) with varying immune functions and mechanisms, depending on the adipose depot type and location. The heterogeneity of B cells and their functions affect the immunometabolism of the adipose tissue in aging and age‐associated metabolic disorders. B cells exist in categorizations of subsets that have developmental or phenotypic differences with varying functionalities. Subsets can be categorized as either protective or pathogenic depending on their secretion profile or involvement in metabolic maintenance. In this article, we summarized recent finding on the B cell heterogeneity and discuss how we can utilize our current knowledge of adipose resident B lymphocytes for potential treatment for age‐associated metabolic disorders. © 2022 American Physiological Society. Compr Physiol 12: 4133–4145, 2022.

Figure 1. Figure 1. The differences in immune cell heterogeneity alterations in inflamed adipose tissue. (A) Homeostasis in adipose tissue is helped maintained through the secretion of anti‐inflammatory molecules IL‐10 and IgM by B‐1a, B‐1b, and regulatory B cell subsets. (B) The immune cell population alters to a pro‐inflammatory phenotype in adipose tissue during inflammation. Adipocyte expansion promotes inflammation of the adipose tissue through the recruitment of M1 polarized macrophages, CD8 T cells, and CD4 T cells. The expansion of B‐2, age‐associated B cells, and aged adipose B cells are hypothesized to contribute to the inflammatory response and subsequent metabolic dysregulation of the tissue.
Figure 2. Figure 2. B cell subsets in adipose tissue can be classified as protective or pathogenic subsets based on their secretory profile. (A) The protective B cell subsets are B‐1a, B‐1b, and regulatory B cells and have been characterized to suppress inflammatory responses and help maintain tissue homeostasis through the release of anti‐inflammatory molecules IL‐10 and IgM. (B) The pathogenic B cell subsets are B‐2, age‐associated B cells (ABCs), and aged adipose B cells (AABs) and have been observed in aging adipose tissue. The secretion of pro‐inflammatory cytokines and autoreactive antibody IgG has demonstrated rapid localized inflammatory damage to adipose tissue.
Figure 3. Figure 3. Potential clinical therapeutic opportunities utilizing B cells. To treat the adverse effects of obesity such as inflammation, insulin resistance, and glucose tolerance, therapeutic options targeting B cells could be a potential treatment. This could include depleting B cells through antibody treatments to prevent damage or transferring protective B cells, such as Bregs or B‐1 cells, from healthy subjects to obese subjects to ameliorate the adipose tissue.


Figure 1. The differences in immune cell heterogeneity alterations in inflamed adipose tissue. (A) Homeostasis in adipose tissue is helped maintained through the secretion of anti‐inflammatory molecules IL‐10 and IgM by B‐1a, B‐1b, and regulatory B cell subsets. (B) The immune cell population alters to a pro‐inflammatory phenotype in adipose tissue during inflammation. Adipocyte expansion promotes inflammation of the adipose tissue through the recruitment of M1 polarized macrophages, CD8 T cells, and CD4 T cells. The expansion of B‐2, age‐associated B cells, and aged adipose B cells are hypothesized to contribute to the inflammatory response and subsequent metabolic dysregulation of the tissue.


Figure 2. B cell subsets in adipose tissue can be classified as protective or pathogenic subsets based on their secretory profile. (A) The protective B cell subsets are B‐1a, B‐1b, and regulatory B cells and have been characterized to suppress inflammatory responses and help maintain tissue homeostasis through the release of anti‐inflammatory molecules IL‐10 and IgM. (B) The pathogenic B cell subsets are B‐2, age‐associated B cells (ABCs), and aged adipose B cells (AABs) and have been observed in aging adipose tissue. The secretion of pro‐inflammatory cytokines and autoreactive antibody IgG has demonstrated rapid localized inflammatory damage to adipose tissue.


Figure 3. Potential clinical therapeutic opportunities utilizing B cells. To treat the adverse effects of obesity such as inflammation, insulin resistance, and glucose tolerance, therapeutic options targeting B cells could be a potential treatment. This could include depleting B cells through antibody treatments to prevent damage or transferring protective B cells, such as Bregs or B‐1 cells, from healthy subjects to obese subjects to ameliorate the adipose tissue.
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Nicole C. Fernandez, Kosaku Shinoda. The Role of B Lymphocyte Subsets in Adipose Tissue Development, Metabolism, and Aging. Compr Physiol 2022, 12: 4133-4145. doi: 10.1002/cphy.c220006