Abstract
Autoantibodies can be either harmful or beneficial to the body. The beneficial autoantibodies play important roles in immunosurveillance, clearance of body waste and maintenance of immune homeostasis. Despite their importance, however, people’s knowledge on the protective autoantibodies is still very limited. In the current study, we examined two autoantibodies that recognized epitopes with only one amino acid. One was against mono-methylated lysine (Kme) and the other was against tri-methylated lysine (Kme3). We found that the antibodies were highly specific and not polyreactive. They did not cross-react each other. Although anti-Kme antibodies were IgM only, a large proportion of the anti-Kme3 antibodies were switched to the IgG isotype. Mass spectrometric analysis showed that both of the antibodies were mainly derived from IGHV 3–7 and/or IGHV3-74 germ line genes with conserved CDR2. De novo sequencing showed that there was a mutation at either of the SS positions on the CDR1 region, which changed one of the serine residues to a basic amino acid, i.e., arginine or lysine. We also found that neither of the antibodies was expressed at birth, and their earliest appearance was approximately 5 months after birth. All healthy human beings expressed the antibodies when they reached age two and maintained the expression thereafter throughout their life. Patients with systemic lupus erythematosus had lower levels of the IgM isotype antibodies. Serum levels of the two IgM antibodies were closely correlated, implying that they were produced by cells from the same B cell subset. We also found that both anti-Kme and anti-Kme3 antibodies could bind and might take part in the clearance of neutrophil extracellular traps released from activated cells. In conclusion, although anti-Kme and anti-Kme3 antibodies share many similarities in their origins, they are different antibodies and have different characteristics.
Highlights
Autoantibodies are antibodies that react to body self components
Column, and the amounts of antibodies obtained from the GGKGGSGGSGGSGC and then with lysine monomethylated GGK (GGKme) and GGKme3 columns on average were 75 μg and 110 μg, respectively
Almost all antibodies eluted from the GGKme column were of the IgM isotype that could be detected by both anti-IgM and anti-J-chain antibodies (Fig 1A)
Summary
Autoantibodies are antibodies that react to body self components. They can be divided into natural antibodies and immune antibodies. Natural autoantibodies (NAAs) are produced without exogenous antigen stimulation [1]. They can be detected in cord blood and in mice housed under germ-free conditions and fed an antigen-free diet [2]. NAAs are usually of the IgM isotype and are polyreactive, which means that they can bind several unrelated antigens with moderate affinity [3]. Immune autoantibodies are produced in response to foreign antigens and become self-reactive by mechanisms such as molecular mimicry and epitope spreading [4]. B cells in primary immune responses produce antibodies mainly of the IgM isotype, and they switch to IgG and other antibody isotypes during secondary and subsequent immune responses
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