Clonal redemption and clonal anergy as mechanisms to balance B cell tolerance and immunity

Abstract

The adaptive immune system is tasked with producing antibodies that recognize a wide scope of potential pathogens, including those never before encountered, and concurrently avoiding formation of antibodies binding host tissues. The diverse repertoire of antibodies produced by V(D)J recombination inevitably includes autoantibodies that bind to self‐antigens, estimated to be as much as 70% of nascent antibodies on immature B cells. Early theoretical models of tolerance hypothesized that such self‐reactive clones could not possibly be allowed to survive and mature. However from the first direct view of the fate of nascent B cells carrying a self‐binding antibody it was clear that many “forbidden clones” circulate to secondary lymphoid tissues, where they adopt an IgMlow IgD+ cell surface phenotype and are prevented from secreting autoantibodies by a series of tolerance checkpoints referred to as “clonal anergy.” Since anergic B cells can be reactivated to secrete pathogenic autoantibodies in certain settings, the advantage of controlling self‐reactive antibodies by clonal anergy has until recently remained enigmatic. Here we review this topic and recent advances showing that anergic B cells are recruited into the germinal center to mutate away from self‐reactivity, undergoing “clonal redemption” into cells making antibodies with exquisite specificity for foreign immunogens.

Serum alpha-mannosidase as an additional barrier to eliciting oligomannose-specific HIV-1-neutralizing antibodies

“…Indeed, experimental evidence suggests that a sustained presence of envelope glycoprotein with the 'proper' glycosylation during weeks or months of infection might trigger the 'right' B cells 51,52 . Of course, we do not know which form(s) of the envelope glycoprotein trigger(s) the development of oligomannose-specific bnAbs during infection 53 or whether the triggered B cells are nominally autoreactive or anergic 54 . Further investigations, perhaps such as done for antibodies to the membrane-proximal region of gp41 55 , may help to answer these questions.…”

Serum alpha-mannosidase as an additional barrier to eliciting oligomannose-specific HIV-1-neutralizing antibodies

“…51,52 . Of course, we do not know which form(s) of the envelope glycoprotein trigger(s) the development of oligomannose-specific bnAbs during infection 53 or whether the triggered B cells are nominally autoreactive or anergic 54 . Further investigations, perhaps such as done for antibodies to the membrane-proximal region of gp41 55 , may help to answer these questions.…”

Seminal plasma protein networks and enriched functions in varicocele: Effect of smoking

“…The prostaglandins act directly on the inflammatory response, leading to vasodilation, oedema and contraction/relaxation of the vascular smooth muscle (Tallima & El Ridi, 2018). The inflammation offers important signals that activate lymphocytes T and B, initiating the specific immune response, leading to the production and release of antibodies to the milieu (Akira, Uematsu, & Takeuchi, 2006; Burnett, Reed, Christ, & Goodnow, 2019). This inflammatory state from cigarette components seems to act in a joint with the impaired blood flow/stasis that are present in varicocele, leading to the overexpression of immune proteins.…”