Pre-B cell loss in senescence coincides with preferential development of immature B cells characterized by partial activation and altered Vh repertoire

Wilson, Emily L.; King, Anne M.; Sherwood, Erin M.; Riley, Richard L.

doi:10.1016/j.exger.2004.11.005

Cited by 15 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously described, these also show increased usage of VhS107.1 33 , a commonly used Vh gene for encoding anti-PC antibodies, and have, not surprisingly, increased reactivity with PC antigen as discussed below. This suggests that even as pre-B and immature B cells in general are diminished in old bone marrow, the capacity to produce new B cells which undergo activation, and express CD43/S7 and also CD23, remains relatively intact.…”

Section: Resultssupporting

confidence: 55%

“…Optimal CD43/S7 expression on immature B cells, like CD23, requires Btk, and consequently BCR signaling 38 . We have previously reported that CD43/S7 is more prevalent on immature B cells from old mice and that new B cells with CD43/S7 expression are generated more readily from B cell precursors in old mice 19,33 . Together with the finding that CD23 expression is more prevalent on immature B cells from old mice, increased CD43/S7 expression on new B cells in old mice likely represents increased activation of these B cells 19,33 .…”

Section: Resultsmentioning

confidence: 95%

“…This early expression of CD23 by bone marrow immature B cells is a likely consequence of activation, possibly driven via the BCR and antigen selection, and is dependent upon Bruton’s tyrosine kinase (Btk) 35 . We have also described subsets of immature B cells based on differential expression of CD43/S7, which is also associated with activation and Btk expression, and described changes in this population in old age 19,33 .…”

Section: Resultsmentioning

confidence: 99%

“…Cells were stained for surface antigens for immature B cells as described above and for BrdU incorporation with a BD BrdU Flow Kit as previously reported 33 .…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is associated with increased B cell reactivity to phosphorylcholine, but reduced T15 idiotype dominance

Khomtchouk

Alter

Ratliff

et al. 2017

Mechanisms of Ageing and Development

Self Cite

View full text Add to dashboard Cite

In young adult BALB/c mice, antibodies to phosphorylcholine (PC) bearing the T15 (TEPC 15) idiotype confer protection against pneumococcal infections. In old age, even though PC reactive B cells are often increased, the proportion of T15+ antibodies declines. We hypothesize that limited surrogate light chain (SLC) and compromise of the pre-B cell receptor checkpoint in old mice contribute to both reduced new B cell generation and changes in the anti-PC antibodies seen in old age. In old mice: 1) early pre-B cell loss is most pronounced at the preBCR checkpoint; however, the reduced pool of early pre-B cells continues to proliferate consistent with preBCR signaling; 2) increased PC reactivity is seen in bone marrow immature B cells; 3) deficient SLC promotes increased B cell PC reactivity and diminished T15 idiotype within a subset of young adult mice; and 4) in old mice, as pre-B cell losses and reduced SLC become progressively more severe, increased T15 negative PC reactive B cells occur. These results associate a reduction in pre-B cells, imposed at the preBCR checkpoint, with increased reactivity to PC, but more limited expression of the protective T15 idiotype among PC reactive antibodies in old age.

show abstract

Section: Resultssupporting

confidence: 55%

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

“…Cells were stained for surface antigens for immature B cells as described above and for BrdU incorporation with a BD BrdU Flow Kit as previously reported 33 .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is associated with increased B cell reactivity to phosphorylcholine, but reduced T15 idiotype dominance

Khomtchouk

Alter

Ratliff

et al. 2017

Mechanisms of Ageing and Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been suggested that age-related differences in repertoire can occur at immature developmental stages in mice [57], although repertoire analysis of bone marrow samples has yet to be performed. In view of the normal clonal expansion that occurs in antigen-experienced cells and skews the repertoire (Figure 2) it is clear that a change in the proportion of naïve:memory B cell subsets, as discussed above, will result in a changed overall repertoire.…”

Section: Figurementioning

confidence: 99%