Lineage tracing reveals B cell antibody class switching is stochastic, cell-autonomous, and tuneable
Journal Title
Immunity
Publication Type
epub ahead of print
Abstract
To optimize immunity to pathogens, B lymphocytes generate plasma cells with functionally diverse antibody isotypes. By lineage tracing single cells within differentiating B cell clones, we identified the heritability of discrete fate controlling mechanisms to inform a general mathematical model of B cell fate regulation. Founder cells highly influenced clonal plasma-cell fate, whereas class switch recombination (CSR) was variegated within clones. In turn, these CSR patterns resulted from independent all-or-none expression of both activation-induced cytidine deaminase (AID) and IgH germline transcription (GLT), with the latter being randomly re-expressed after each cell division. A stochastic model premised on these molecular transition rules accurately predicted antibody switching outcomes under varied conditions in vitro and during an immune response in vivo. Thus, the generation of functionally diverse antibody types follows rules of autonomous cellular programming that can be adapted and modeled for the rational control of antibody classes for potential therapeutic benefit.
Publisher
Elsevier
Keywords
B lymphocyte; antibody; differentiation; isotype; mathematical model
WEHI Research Division(s)
Immunology
PubMed ID
36108634
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2022-09-19 02:39:10
Last Modified: 2022-09-23 09:43:53
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