The B‐cell system of human mucosae and exocrine glands

Per Brandtzaeg; Inger Nina Farstad; Finn‐Eirik Johansen; H Craig Morton; Inger Natvig Norderhaug; Takeshi Yamanaka; Per Brandtzaeg; Inger Nina Farstad; Finn‐Eirik Johansen; H Craig Morton; Inger Natvig Norderhaug; Takeshi Yamanaka

doi:10.1111/j.1600-065X.1999.tb01342.x

. 2006 Apr 28;171(1):45–87. doi: 10.1111/j.1600-065X.1999.tb01342.x

The B‐cell system of human mucosae and exocrine glands

Per Brandtzaeg ¹, Inger Nina Farstad ¹, Finn‐Eirik Johansen ¹, H Craig Morton ¹, Inger Natvig Norderhaug ¹, Takeshi Yamanaka ¹, Per Brandtzaeg ^1,^✉, Inger Nina Farstad ¹, Finn‐Eirik Johansen ¹, H Craig Morton ¹, Inger Natvig Norderhaug ¹, Takeshi Yamanaka ¹

PMCID: PMC7159139 PMID: 10582165

Abstract

Summary: The mucosae and exocrine glands harbour the largest activated B‐cell system of the body, amounting to some 80–90% of all immunoglobulins (Ig)‐producing cells. The major product of these immunocytes is polymeric (p)IgA (mainly dimers) with associated J chain. Both pIgA and pentameric IgM contain a binding site for the polymeric Ig receptor (pIgR), or secretory component (SC), which is a requirement for their active external transport through secretory epithelia. The pIgR/SC binding site depends on covalent incorporation of the J chain into the quaternary structure of the polymers when they are produced by the local immunocytes. This important differentiation characteristic appears to be sufficient functional justification for the J chain to be expressed also by most B cells terminating at secretory effector sites with IgD or IgG production; they probably represent a ‘spin‐off’ from sequential downstream C_H switching on its way to pIgA expression, thus apparently reflecting a maturational stage of effector B‐cell clones compatible with homing to these sites. Observations in IgA‐deficient individuals suggest that the magnitude of this homing is fairly well maintained even when the differentiation pathway to IgA is blocked. Certain microenvironmental elements such as specific cytokines and dendritic cells appear to be required for induction of IgA synthesis, but it remains virtually unknown why this isotype normally is such a dominating product of local immunocytes and why they have such a high level of J chain expression. Also, despite the recent identification of some important requirements in terms of adhesion molecules (e.g. integrin α4β7 and MAdCAM‐1) that explain the “gut‐seeking” properties of enterically induced B cells, the origin of regionalized homing of B cells to secretory effector sites outside the gut remains elusive. Moreover, little is known about immune regulation underlying the striking disparity of both the class (IgD, IgM) and subclass (IgA1, IgA2, IgGI, IgG2) production patterns shown by local iinmttnocytes in various regions of the body, although the topical microbiota and other environmental stimuli might be important. Rational design of local vaccines will depend on better knowledge of both inductive and migratory properties of human mucosal B cells.

Acknowledgements This work was supported by the Norwegian Cancer Society, the Research Council of Norway, and Anders Jahre's Foundation. Ms. Hege Eliassen Bryne and Mr Erik Kulø Hagen are gratefully acknowledged for excellent assistance with the manuscript.

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PERMALINK

The B‐cell system of human mucosae and exocrine glands

Per Brandtzaeg

Inger Nina Farstad

Finn‐Eirik Johansen

H Craig Morton

Inger Natvig Norderhaug

Takeshi Yamanaka

Per Brandtzaeg

Inger Nina Farstad

Finn‐Eirik Johansen

H Craig Morton

Inger Natvig Norderhaug

Takeshi Yamanaka

Abstract

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PERMALINK

The B‐cell system of human mucosae and exocrine glands

Per Brandtzaeg

Inger Nina Farstad

Finn‐Eirik Johansen

H Craig Morton

Inger Natvig Norderhaug

Takeshi Yamanaka

Per Brandtzaeg

Inger Nina Farstad

Finn‐Eirik Johansen

H Craig Morton

Inger Natvig Norderhaug

Takeshi Yamanaka

Abstract

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