CD1high B cells: a population of mixed origin

Abstract

A specialized subpopulation of T lymphocytes is reactive to the MHC class I‐like molecule CD1d. It is not clear which cells are the major antigen‐presenting cells in vivo in the activation of CD1‐restricted immune responses. We have characterized a subset of B lymphocytes expressing six‐ to eightfold higher levels of CD1 than the bulk of B cells. The cells have a surface phenotype (CD21high, CD23low, IgMhigh, IgDlow) found previously to characterize B cells residing in the splenic marginal zones. CD1high B cells localize preferentially to the spleen, and appear late in ontogeny, at 3 – 4 weeks of age. The CD1high B cells were present in mice lacking conventional helper T cells, ruling out an exclusive origin from T cell‐dependent immune responses. Still, some CD1high B cells had been involved in T cell‐dependent immune responses as suggested by mutations in their rearranged immunoglobulin gene regions. The population could still be found in mice with severely reduced B cell reactivity to bacterial lipopplysaccharides (C3H / HeJ mice) and in mice unable to respond to thymus‐independent type 2 antigens (NFR.Xid mice), as well as in germ‐free mice, indicating that bacterial antigens are not major stimuli for the induction of CD1high B cells. In contrast, the CD1high B cell population was severely reduced in CD19‐deficient mice. Taken together, the results imply that the CD1high population is heterogenous and of mixed origin, dependent for its development or maintenance on signaling through the CD19 molecule.

Analysis of Marginal Zone B Cell Development in the Mouse with Limited B Cell Diversity: Role of the Antigen Receptor Signals in the Recruitment of B Cells to the Marginal Zone

“…In CBA/N mice with a Xid phenotype, there was a marked decrease in the number of FO B cells, while the number of MZ B cells was affected to a lesser extent (12,14,19). Thus, the proportion of MZ B cells apparently increased in these mice.…”

“…2, 10, and 11). Although the origin of MZ B cells remains controversial, newly formed (NF) B cells are most likely the immediate precursors (12)(13)(14)(15), while an origin from FO B cells is also suggested (16,17). Accumulating evidence indicates that MZ B cells may be positively selected by BCR signals that might be distinct from those required for generating FO B cells.…”

“…Stimulation with autologous Ags or endogenous microfloras might play a role in the positive selection of MZ B cells (2). In addition, gene knockouts of positive regulators for BCR signaling, including CD19, impaired the development of MZ B cells without markedly affecting the generation of FO B cells (10,13,14). In contrast, the dysfunction of Bruton's tyrosine kinase (Btk) that is an essential component of the BCR signalosome led to defects in the development of FO B cells with the MZ B cell compartment being intact (12,14).…”

“…In addition, gene knockouts of positive regulators for BCR signaling, including CD19, impaired the development of MZ B cells without markedly affecting the generation of FO B cells (10,13,14). In contrast, the dysfunction of Bruton's tyrosine kinase (Btk) that is an essential component of the BCR signalosome led to defects in the development of FO B cells with the MZ B cell compartment being intact (12,14). Although an optimal strength of BCR signals tuned by positive and negative regulators may be favorable for the generation of MZ B cells (11)(12)(13)19), a model remains to be established that can accommodate contradictory data from knockout lines for BCR signaling.…”

ICOS‐dependent stimulation of NKT cells by marginal zone B cells

“…Moreover, MZ B cells have been shown to continuously shuttle between MZ and white pulp, which allows them to transport antigens into the follicles [3]. Remarkably, when compared to other mouse APCs, MZ B cells were found to express high levels of CD1d, the non-classical MHC I molecule responsible for presentation of lipid or glycolipid antigens to NKT cells [4][5][6][7].The major subset of CD1d-restricted murine NKT cells (invariant or type I) expresses a semi-conservative T-cell receptor (TCR) consisting of Va14-Ja18 in conjunction with Vb8.2, Vb7 or Vb2 (7,8,16). This population is able to recognize the glycolipid ligand a-galactosylceramide (aGalCer) bound to CD1d.…”