Residues that mediate DNA binding of autoimmune antibodies.

Radic, Marko; Mackle, J J; Erikson, Jan; Mol, Clifford D.; Anderson, W.F.; Weigert, Martin

doi:10.4049/jimmunol.150.11.4966

Cited by 252 publications

(16 citation statements)

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“…Changes in amino acid use within the CDR-H3 are indicative of selection over time. Increase in arginine use is associated with an increase in autoreactive antibodies ( 44 , 57 , 58 ). Herein, we demonstrate female peritoneal PtC+CD5+ B-1 cells have an increase in arginine use with age, suggesting this population could contribute to a corresponding increase in autoantibodies during aging.…”

Section: Discussionmentioning

confidence: 99%

Age-related changes in antigen-specific natural antibodies are influenced by sex

et al. 2023

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IntroductionNatural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis. CD5+ B-1 cell-derived NAbs have a unique germline-like structure that lacks N-additions, a feature critical for providing protection against infection. Previously, we demonstrated the repertoire and germline status of PtC+CD5+ B-1 cell IgM obtained from male mice changes with age depending on the anatomical location of the B-1 cells. More recently, we demonstrated serum antibody from aged female mice maintains protection against pneumococcal infection, whereas serum antibody from male mice does not provide protection.ResultsHere, we show that aged female mice have significantly more splenic PtC+CD5+ B-1 cells and more PtC specific serum IgM than aged male mice. Furthermore, we find both age and biological sex related repertoire differences when comparing B cell receptor (BCR) sequencing results of PtC+CD5+ B-1 cells. While BCR germline status of PtC+CD5+ B-1 cells from aged male and female mice is similar in the peritoneal cavity, it differs significantly in the spleen, where aged females retain germline configuration and aged males do not. Nucleic acid sensing toll-like receptors are critical in the maintenance of PtC+ B-1 cells; therefore, to begin to understand the mechanism of differences observed between the male and female PtC+CD5+ B-1 cell repertoire, we analyzed levels of cell-free nucleic acids and found increases in aged females.ConclusionOur results suggest the antigenic milieu differs between aged males and females, leading to differential selection of antigen-specific B-1 cells over time. Further elucidation of how biological sex differences influence the maintenance of B-1 cells within the aging environment will be essential to understand sex and age-related disparities in the susceptibility to bacterial infection and will aid in the development of more effective vaccination and/or therapeutic strategies specific for males and females.

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Section: Discussionmentioning

confidence: 99%

Age-related changes in antigen-specific natural antibodies are influenced by sex

et al. 2023

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“…The changes observed in amino acid use within the CDR-H3 provide clues to how these populations are selected over time. An increase in arginine use is associated with an increase in autoreactive antibodies (47,53,54). Herein, we demonstrate peritoneal PtC+ B-1a, peritoneal PtC-B-1a, and splenic PC+ B-1a cells have an increase in arginine use with age, suggesting these populations could contribute to an increase in autoantibodies with age.…”

Section: Hydrophobicity and Amino Acid Composition Of The Cdr-h3 Loop...mentioning

confidence: 64%

Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age

Holodick

Tsuji

Rothstein

2020

The Journal of Immunology

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B-1a cells provide immediate and essential protection from infection through production of natural immunoglobulin, which is germline-like due to minimal insertion of N-region additions. We have previously demonstrated peritoneal B-1a cell derived phosphorylcholine (PC)-specific and total IgM moves away from germline (as evidenced by an increase in N-additions) with age as a result of selection. In young mice, anti-phosphatidylcholine (PtC) antibodies, like anti-PC antibodies, contain few N-additions, and have been shown to be essential in protection from bacterial sepsis. Herein, we demonstrate the germline-like status of PtC specific peritoneal B-1a cell IgM does not change with age. In direct contrast, the splenic PtC-binding B-1a cell population does not preserve its IgM germline status in the aged. Furthermore, splenic PtC-binding B-1a cells displayed more diverse VH use in both the young and aged as compared to peritoneal PtC-binding B-1a cells. While both peritoneal and splenic PtC-binding populations increase VH12 use with age, differential use of VH11 and VH2 is observed between these populations with age. These results suggest disparate selection pressures occur with age upon B-1a cells expressing different specificities in distinct locations. Overall, these results illuminate the need to further elucidate how B-1a cells are influenced over time in terms of production and selection, both of which contribute to the actual and available natural IgM repertoire with increasing age. Such studies would aid in the development of more effective vaccination and therapeutic strategies in the aged population.

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“…[13,15] Light chains are signi cant modulators of antibody speci city. [16,17] Self reactive antibodies are turned into non harmful antibodies by light chains. In allergic disoders light chains activate mast cells.…”

Section: Discussionmentioning

confidence: 99%

Intermittent Fasting Improves Some Serum Proteins: a Study on Rats Model

Danladi

Serakinci

Ivanovich³

et al. 2023

Preprint

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Backgroud: There are approximately 100,000 proteins in humans with various physiological functions. The study of proteome in relation to calorie intake is expected to play an important role in solving major aging-associated problems in humans, such as obesity, diabetes, cardiovascular disease and cancer. Objective: To study the changes in serum proteins in young and old rats that were intermittently fasted. Method: 3 and 19 months old rats were intermittently fasted, Every 48 hours. The weights of both young and old rats were taken before feeding, while the young rats received 4g per 100g of body mass the adult rats received 1.75g per 100g of body mass for 14 days. Consecutively both young and old rats received a fattening ration of 25g feed ad lithium every 24 hours irrespective of age for 14 days. Throughout the experiment, animals were kept in individual cages with free access to water. Blood samples were collected after cervical dislocation. The blood serum was then analysed on SDS-PAGE electrophoresis. Results: Apolipoprotein A1 sharply increased in young rats during refeeding periods. Immunoglobulin light chains (lambda and kappa) levels increased during starvation in young rats. Apolipoprotein E levels in young animals was initially high during first cycle of starvation, Also In young animals alpha1-macroglobulin was observed to be high following starvation. In young animals apoA-4 increased during the first cycle of feeding. In young animals the levels of alpha1-antitrypsin flunctuated between the period of starvation and feeding, With higher levels been observed during starvation. In old rats after the first, Second intermittent fasting and second refeeding, Apo E, Apo A-4 and Apo A1 increased, While other serum proteins remained suppressed. Conclusion: The intermittent fasting in young and adult experimental animals, induced adaptive stress by upregulating and downregulating some serum proteins.

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Residues that mediate DNA binding of autoimmune antibodies.

Cited by 252 publications

References 0 publications

Age-related changes in antigen-specific natural antibodies are influenced by sex

Age-related changes in antigen-specific natural antibodies are influenced by sex

Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age

Intermittent Fasting Improves Some Serum Proteins: a Study on Rats Model

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