INTRODUCTION
It is instructive to categorize various tissue compartments involved in mucosal immunity according to their main function. However, until recently, there was no consensus in the scientific community as to how these compartments should be named and classified. This lack of standardized terminology has been particularly confusing for newcomers to the mucosal immunology field. To address this issue, the Nomenclature Committee of the Society for Mucosal Immunology, under its chair Michael W. Russell, recommended adoption of a standard nomenclature initially proposed by Brandtzaeg and Pabst in 2004. 1 This terminology was unanimously approved by the Society for Mucosal Immunology ’ s General Assembly at the 13th ICMI in Tokyo, 2007. This paper delineates this recommended nomenclature, with the primary aim of improving communication about the anatomy of the mucosal immune system. Before addressing this recommendation, however, we would like to recapitulate the previously proposed nomenclature for molecules related to the secretory immunoglobulin A (SIgA or S-IgA) system. This seems to be necessary as the proper terminology is often neglected by many immunologists — and even by many major journals of immunology.
RECOMMENDED NOMENCLATURE FOR SECRETORY IMMUNE-FUNCTION MOLECULES
The molecular specialization of the SIgA system was described as early as in 1965, 2 and a common epithelial transport model for dimers (and larger polymers) of IgA and pentamers of IgM was proposed in 1974. 3,4 The epithelial glycoprotein designated secretory component (SC) by WHO in 1972 (previously called “ transport piece ” or “ secretory piece ” ) turned out to be responsible for the receptor-mediated transcytosis of J-chain-containing Ig polymers (pIgs) through secretory epithelia, 5 and the functional name polymeric Ig receptor (pIgR) is now commonly used for the transmembrane form of SC.
During export of pIgs, the cleaved ectodomain of the pIgR is incorporated into SIgA and secretory IgM as the so-called bound SC, which stabilizes particularly SIgA by covalent bonding, or is released from unoccupied receptor into secretions as free SC. Bound and free SC can be distinguished by conformational epitopes 6 and may in different ways exhibit innate immune functions. 7 SC thus exists in three forms with distinct functional roles. The terminology of the SIg system ( Table 1 ) was approved by the Society for Mucosal Immunology in 1997 and also by the IUIS / WHO Nomenclature Committee. 8 The awareness and proper use of this nomenclature will be important for eliminating confusion when discussing this system, examples of which are the still common use of a small “ s ” (which stands for “ surface ” ) as prefix for the SIgs, and the often neglected specification of SC as being either bound or free in distinction from mem brane SC.
RECOMMENDED NOMENCLATURE FOR MUCOSAASSOCIATED IMMUNE-CELL COMPARTMENTS
Inductive and effector tissues No attempt has been made previously to standardize the terminology applicable to the various tissue compartments involved in the mucosal immune system. These compartments can principally be divided into inductive sites — where antigens sampled from mucosal surfaces stimulate cognate naive T and B lymphocytes — and effector sites — where the effector cells after extravasation, retention, and differentiation perform their action, for instance by contributing to the formation of SIgA antibodies ( Figures 1 and 2 ). The inductive sites for mucosal immunity are constituted by organized mucosa-associated lymphoid tissue (MALT) as well as local / regional mucosa-draining lymph nodes (LNs), whereas the effector sites consist of distinctly different histological compartments — including the lamina propria (LP) of various mucosae, the stroma of exocrine glands, and surface epithelia. 1 Peyer ’ s patches (PPs) in the small intestine of humans, rodents, and rabbits are typical MALT structures believed to be a main source of conventional (B2) surface (s)IgA-expressing primed (memory / effector) and class-switched mucosal B cells. 9,10 The term MALT was first coined to emphasize that solitary organized mucosa-associated B-cell follicles and larger lymphoid aggregates have common features and are the origin of cells that traffic to mucosal effector sites. 11 MALT is sub-divided according to anatomical regions ( Table 2 ), and the distribution and composition of such lymphoid structures vary considerably with species ( Figure 3 ). Also the age and tissue state (normal or chronically inflamed) have an impact on the appearance of MALT. In contrast to PPs and tonsils, other human MALT structures do not apparently develop prenatally, 1 and their occurrence and size generally depend on induction by exogenous stimuli. For instance, bronchus-associated lymphoid tissue (BALT) is not regularly found in normal lungs of adults — reportedly being absent also in 60 % of healthy adolescents and children. 12 It should be noted that although LP is considered an effector site, it is still important for the expansion of B cells and their terminal differentiation to plasma cells (PCs). 9 In addition, T-cell-independent switch of B cells to IgA expression has been reported to occur in murine LP. 10 This event may particularly involve the large contingent of B1 cells derived from the peritoneal cavity in mice — a possibility that remains controversial, however, because of discrepant findings. 1,13 No evidence exists to suggest that B1 cells populate significantly human gut mucosa, 1,9 and no convincing signs of class switch to IgA have previously been found in normal human intestinal LP. 14 Nevertheless, in the large bowel, bacteria could induce switch factors in epithelial cells and LP dendritic cells (DCs) that may drive T-cell-independent B-cell development toward the IgA2 subclass. 15 The first evidence for such a role of the gut microbiota was obtained as early as in 1995 by showing that jejunal segments with bacterial overgrowth had an ~ 50 % reduction of the IgA1:IgA2 mucosal PC ratio. 16 Finally, expansion of memory / effector T cells can apparently take place within the surface epithelium, which is often referred to as the intraepithelial lymphocyte (IEL) compartment ( Table 2 ). There is considerable “ cross talk ” both within and between the LP and IEL compartments. 17