TY - JOUR
T1 - Identification and Characterization of Adipose Tissue-Derived Human Antibodies With “Anti-self” Specificity
AU - Frasca, Daniela
AU - Diaz, Alain
AU - Romero, Maria
AU - Garcia, Denisse
AU - Jayram, Diya
AU - Thaller, Seth
AU - del Carmen Piqueras, Maria
AU - Bhattacharya, Sanjoy
AU - Blomberg, Bonnie B.
PY - 2020/2/28
Y1 - 2020/2/28
N2 - We have previously shown that the human obese adipose tissue (AT) contributes to increased secretion of adipocyte-specific IgG antibodies in individuals with obesity. This occurs without any exogenous stimulation, because the ongoing process of cell death in the obese AT leads to the release of “self” antigens able to induce chronic stimulation of B cells. We have identified several mechanisms responsible for the release of “self” antigens, such as hypoxia, cell cytotoxicity, and DNA damage. In this paper, we confirm and extend our initial observation on a different cohort of individuals, and we show that also the plasma of these individuals is enriched in IgG antibodies with specificities for adipocyte-derived antigens. Adipocyte-specific IgG secreted in the obese AT are significantly correlated with those present in plasma. Using immunoprecipitation and mass spectrometry, we have identified these antigenic specificities. The antigens are almost exclusively intracellular or cell-associated, usually not recognized as “self” antigens, but they are released by cells dying in the AT. We also show for the first time that the adipocytes in the obese AT contribute to the secretion of IgG autoimmune antibodies and this seems to be due to their expression of the antigen-presenting molecules CD1d and, to a much lesser extent, MHC class II, as our mechanistic experiments performed in mice have shown. These results may lead to the development of novel therapeutic strategies to control autoimmunity.
AB - We have previously shown that the human obese adipose tissue (AT) contributes to increased secretion of adipocyte-specific IgG antibodies in individuals with obesity. This occurs without any exogenous stimulation, because the ongoing process of cell death in the obese AT leads to the release of “self” antigens able to induce chronic stimulation of B cells. We have identified several mechanisms responsible for the release of “self” antigens, such as hypoxia, cell cytotoxicity, and DNA damage. In this paper, we confirm and extend our initial observation on a different cohort of individuals, and we show that also the plasma of these individuals is enriched in IgG antibodies with specificities for adipocyte-derived antigens. Adipocyte-specific IgG secreted in the obese AT are significantly correlated with those present in plasma. Using immunoprecipitation and mass spectrometry, we have identified these antigenic specificities. The antigens are almost exclusively intracellular or cell-associated, usually not recognized as “self” antigens, but they are released by cells dying in the AT. We also show for the first time that the adipocytes in the obese AT contribute to the secretion of IgG autoimmune antibodies and this seems to be due to their expression of the antigen-presenting molecules CD1d and, to a much lesser extent, MHC class II, as our mechanistic experiments performed in mice have shown. These results may lead to the development of novel therapeutic strategies to control autoimmunity.
KW - B cells
KW - adipocytes
KW - adipose tissue
KW - antigen presentation
KW - autoimmune antibodies
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U2 - 10.3389/fimmu.2020.00392
DO - 10.3389/fimmu.2020.00392
M3 - Article
C2 - 32184790
AN - SCOPUS:85082033744
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 392
ER -