Publication Date
2014
Journal Title
J Immunol
Abstract
Natural Abs produced by B-1a cells are required for immediate protection against infection. The protective capacity of natural Abs is attributed to germline-like structure, which includes the relative absence of N-region addition. Previous studies have shown B-1a cell Ig from aged mice contains abundant nontemplated (N)-additions. B-1a cells have been shown to derive from a specific lineage-negative (Lin(-)) CD45R(low/-) CD19(+) progenitor found both in fetal liver and adult bone marrow. In this study, we report identification of a fetal liver population characterized phenotypically as Lin(-)CD45R(-)CD19(-), which gives rise to IgM(+)IgD(low)CD45R(low)CD5(+)Mac-1(+)CD19(high)CD43(+)CD23(low) B-1a cells upon adoptive transfer to SCID recipients. These B-1a cells derived from the Lin(-)CD45R(-)CD19(-) fetal liver population produce natural Ab that binds pneumococcal Ags, but this Ig contains substantial N-addition despite initial absence of TdT. Furthermore, we show extensive N-addition is also present in B-1a cells derived from the Lin(-)CD45R(low/-)CD19(+) B-1 progenitor found in the bone marrow. Together these results demonstrate B-1a cell N-addition depends on the type of progenitor and the location of the progenitor during its development. These findings have implications for how regulation of different progenitors from fetal liver and bone marrow may play a role in the age-related increase in N-region addition by B-1a cells in normal animals.
Volume Number
192
Issue Number
5
Pages
2432-2441
Document Type
Article
EPub Date
2014/01/31
Status
Faculty; Northwell Researcher
Facility
School of Medicine; Northwell Health
Primary Department
Molecular Medicine
Additional Departments
General Internal Medicine
PMID
DOI
10.4049/jimmunol.1300247