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Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination

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Science  13 Apr 2018:
Vol. 360, Issue 6385, pp. 223-226
DOI: 10.1126/science.aao3859

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  • B cell positive selection: a commentary on Burnett et al. (13 April, p. 223)

    Following the emergence of clonal selection ideas in the 1950s, the development of immune cell repertoires was seen to require the negative selection of self-reacting cells, with remaining cells exhibiting a wide range of essentially non-targeted specificities. Thus, when confronting the universe of possible not-self antigens, formidable in range, a potential host organism spread its resources widely. A proposed differential avidity mechanism, through which an organism could anticipate specificities for coping with microbial pathogens, introduced the less intuitive concept of positive selection. Be they of T or B lineages, immune cells were held to be positively selected for weak reactivity with self determinants (1). While positive selection in developing lineages is now widely accepted for T cells (2-6), its application to developing B cells is less established (7-8).

    In highlighting “the value of retaining self-reactive clones as substrates for protective antibody responses,” Burnett et al. (9) strongly support the case for an initial positive selection of B cells for responsiveness against what have been termed microbial “near-self” antigens (1, 10-12). Moreover, unlike T cells, it is shown that there is then a further germinal center maturation trajectory where, what are termed “almost self” antigens, serve as a starting point for specificity fine-tuning. Thus, self-reactive B cells were directed “down an alternative trajectory, which produced a higher final a...

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    Competing Interests: None declared.