Early development of Ig-secreting cells in young of germ-free BALB/c mice fed a chemically defined ultrafiltered diet

Bos, Nicolaas A.; Meeuwsen, Cornelia G.; Hooijkaas, Herbert; Benner, R.; Wostmann, Bernard S.; Pleasants, Julian R.

doi:10.1016/0008-8749(87)90071-2

Cited by 37 publications

(24 citation statements)

References 24 publications

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“…Although the mechanisms leading to selection and expansion of B-1 cells are unclear, it is now appreciated that antigen selection during the fetal and neonatal period leads to positive selection (11,47,48). Since this appears to occur equally well in mice raised in germ-free environments (35,49,50), this selection is of necessity made by endogenous "self-antigens." This is in contrast to developing, self-reactive B-2 cells, in which such antigen encounter early in life leads to negative selection via apoptosis (a process known as clonal deletion) or anergy.…”

Section: Discussionmentioning

confidence: 99%

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

Chou¹,

Fogelstrand²,

Hartvigsen³

et al. 2009

J. Clin. Invest.

417

452

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

Chou¹,

Fogelstrand²,

Hartvigsen³

et al. 2009

J. Clin. Invest.

417

452

View full text Add to dashboard Cite

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“…The demonstration that Ft-LPS immunization stimulates B-1a cells to produce a specific immune response is somewhat jarring, because B-1 cells are better known as producers of ''innate antibodies'' in conventional and germ-free mice (15,16) than as responders to immunogens. However, as data presented here and in previous studies show, B-1a (6,17) and B-1b (18,19) with appropriate BCR can clearly respond to stimulation with cognate antigens, e.g., B-1a produce T15-idiotype anti-phosphorylcholine (PC) in response to Streptococcus pneumoniae infection (6,17) and B-1b produce antibodies in response to Streptococcus pneumoniae (18) and Borrelia hermsii (19).…”

Section: Discussionmentioning

confidence: 99%

“…For Tindependent responses, reports are equally confounded:, TLR signaling has been shown to induce IgM secretion (25,26), cellular proliferation (25,26), B-1 egress from the PerC (27), and B-1 differentiation into plasma cells (25). However, natural antibodies are produced in germ-free mice (15,16) where TLR signaling from exogenous sources is considered to be minimal.…”

Section: Discussionmentioning

confidence: 99%

Antigen-specific B-1a antibodies induced byFrancisella tularensisLPS provide long-term protection againstF. tularensisLVS challenge

Cole

Yang

Elkins

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

102

137

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“…They have an important role in providing a first line of defense against invading pathogens and as such represent a nonredundant component of the humoral immune system (21). Natural antibodies are predominantly IgM, which is in part established by the fact that serum IgM levels are similar in mice raised under germ-free or antigen-free conditions compared with mice housed under conventional conditions (22)(23)(24). In contrast, serum IgG and IgA levels in these mice are depressed, indicating the greater dependence of these isotypes on antigenic stimulation (25).…”

Section: Role Of B-1 Cells and Natural Antibodies In Innate Immunitymentioning

confidence: 99%

Thematic review series: The Immune System and Atherogenesis. The role of natural antibodies in atherogenesis

Binder

Shaw

Chang

et al. 2005

Journal of Lipid Research

231

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Atherosclerosis is now widely recognized as a chronic inflammatory disease that involves innate and adaptive immune responses. Both cellular and humoral components of the immune system have been implicated in atherogenesis. Natural antibodies can be considered humoral factors of innate immunity, and their functional role in health and disease has been reexamined in recent years. Natural antibodies exhibit a remarkably conserved repertoire that includes a broad specificity for self-antigens. For this reason, they are believed to be a product of natural selection and have been suggested to play an important role in "housekeeping" functions. Recent evidence has revealed that oxidation-specific epitopes are important and maybe immunodominant targets of natural antibodies, suggesting an important function for these antibodies in the host response to consequences of oxidative stress, for example, to the oxidative events that occur when cells undergo apoptosis.

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Early development of Ig-secreting cells in young of germ-free BALB/c mice fed a chemically defined ultrafiltered diet

Cited by 37 publications

References 24 publications

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

Antigen-specific B-1a antibodies induced byFrancisella tularensisLPS provide long-term protection againstF. tularensisLVS challenge

Thematic review series: The Immune System and Atherogenesis. The role of natural antibodies in atherogenesis

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