The human neutrophil-specific alloantigen NB1 was identified as a glycosyl-phosphatidylinositol (GPI)-anchored N-glycosylated protein of M(r) 56-62 kD under reducing conditions. Under non-reducing conditions its M(r) was 49-55 kD. This glycoprotein antigen was found to be expressed by only a subpopulation of normal donor neutrophils, and could not be detected on other blood cells. The allotypic epitope recognized by human anti-NB1 IgG was also recognized by the mouse monoclonal antibody 1B5. The percentage of neutrophils stained by these antibodies varied greatly among healthy donors (range 0-100%). When 16 donors were repeatedly tested, the NB1-positive neutrophil fraction appeared to remain remarkably constant over time in most donors, but significant fluctuations were seen in some. NB1 antigen was found to be expressed not only on the plasma membrane, but also intracellularly on the membranes of small vesicles and specific granules. The neutrophils which expressed NB1 antigen on the plasma membrane were the same as those with intracellular expression of this antigen. Crosslinking of NB1 antigen on the plasma membrane with monoclonal antibody 1B5 and goat-anti-mouse Ig resulted in internalization of the complex, while in-vitro stimulation of neutrophils caused an increase of the intensity of plasma membrane staining with anti-NB1, but only of those cells that were positive already prior to stimulation. The NB1 glycoprotein thus appears to identify a distinct subset of neutrophils, the size of which greatly varies among healthy donors. The function of the NB1 glycoprotein remains unclear, but its behaviour upon crosslinking and chemotactic peptide stimulation suggests a possible role as receptor molecule.

The diverse host defense and immunoregulatory functions of human T cells are performed by phenotypically heterogeneous subpopulations. Among the membrane antigens that are differentially expressed by reciprocal human T-cell subsets are the CD45RA and CD45RO isoforms of the common leukocyte antigen family, which have been hypothesized to identify "naive" and "memory" T cells, respectively. The CD45RA antigen is first expressed by T-lineage cells relatively late during their intrathymic maturation and continues to be expressed by most T cells in the immunologically naive neonate. With increasing age and antigenic exposure, however, CD45RA-/RO+ cells become more prevalent in the circulation and comprise the majority of cells in tissues. Analyses of the functional capabilities of CD4+CD45RA+ and CD4+CD45RO+ cells have shown that proliferative responses to "memory" recall antigens or the ability to provide help for antibody production are functions uniquely performed by CD4+CD45RA-/RO+ cells. The major immunoregulatory functions described for CD4+CD45RA+ cells involve suppression of immune responses, either directly or via the induction of suppressor activity by CD8+ cells. Two general models of differentiation have been proposed to describe the lineal relationship of these T-cell subsets. Although these subsets could represent mature, phenotypically and functionally stable progeny arising from separate differentiation pathways, there is considerable experimental support for the hypothesis that CD45RA-/RO+ cells are "memory" cells that derive from "naive" or "virgin" CD45RA+/RO- precursors via an activation-dependent postthymic differentiation pathway. Altered frequencies of CD45RA+ and CD45RO+ T cells have been observed in a variety of different clinical conditions, particularly diseases manifesting altered immune function. These findings have contributed new information concerning the physiological events regulating the in vivo generation of these T-cell subsets. In addition, they may provide clues to the pathogenetic processes associated with certain diseases.

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