IL-9-Induced Expansion of B-1b Cells Restores Numbers but Not Function of B-1 Lymphocytes in xid Mice

Abstract

Mice expressing the X-linked immunodeficiency (xid) mutation lack functional Bruton’s tyrosine kinase and were shown to be specifically deficient in peritoneal B-1 lymphocytes. We have previously shown that IL-9, a cytokine produced by TH2 lymphocytes, promotes B-1 cell expansion in vivo. To determine whether IL-9 overexpression might compensate the xid mutation for B-1 lymphocyte development, we crossed xid mice with IL-9-transgenic mice. In this model, IL-9 restored normal numbers of mature peritoneal B-1 cells that all belonged to the CD5− B-1b subset. Despite this normal B-1 lymphocyte number, IL-9 failed to restore classical functions of B-1 cells, namely, the production of natural IgM Abs, the T15 Id Ab response to phosphorylcholine immunization, and the antipolysaccharide humoral response against Streptococcus pneumoniae. By using bromelain-treated RBC, we showed that the antigenic repertoire of these IL-9-induced B-1b lymphocytes was different from the repertoire of classical CD5+ B-1a cells, indicating that the lack of B-1 function by B-1b cells is associated with distinct Ag specificities. Taken together, our data show that B-1b cell development can restore the peritoneal B-1 population in xid mice but that these B-1b cells are functionally distinct from CD5+ B-1a lymphocytes.

CD11b expression distinguishes sequential stages of peritoneal B-1 development

“…Cell transfer studies then showed that these populations, also referred to as subsets, are developmentally distinct, in that, each is capable of fully replenishing its niche when sorted and transferred to adoptive recipients and neither has the capability to more than minimally replenish the other (2,5,6). Consistent with this developmental distinction, and with differences noted between the B-1a and B-1b repertoire, recent studies have shown that B-1a and B-1b have distinct immune functions and respond differently to antigenic stimulation (1,(7)(8)(9)(10)(11)(12).…”

Antigen-specific antibody responses in B-1a and their relationship to natural immunity

“…Most recently, foreshadowing studies presented here, we have shown that immunization with FtL, an atypical LPS isolated from Ft LVS, induces B-1a with FtL-binding IgM receptors to appear in spleen and to produce anti-FtL IgM primary antibody responses that protect against lethal Ft LVS challenge (19,20). Consistent with B-1a mediating this protection, FtL priming does not similarly protect Bruton's tyrosine kinase (Btk)-mutant (xid) mice, which have B-1b but lack B-1a (21)(22)(23).…”

IL-13 Mediates In Vivo IL-9 Activities on Lung Epithelial Cells but Not on Hematopoietic Cells

“…B1-b cells preferentially reside in the peritoneal cavity and are characterized by expression of the Mac1 cell surface Ag. Although they share these characteristics with CD5 ϩ B1-a cells, IL-9-activated B1-b cells fail to recapitulate activities ascribed to B1-a cells, including natural IgM and autoantibody production (27,46). Interestingly, in a silica-induced lung fibrosis model, the anti-fibrotic effect of IL-9 correlated with increased B cell numbers in BAL (26) and was lost in B cell-deficient mice (47).…”