IgA1IgA2

IgA1IgA2 refers to the two immunoglobulin A (IgA) heavy-chain subclasses produced by B cells in humans: IgA1 and IgA2. Together, they constitute the major forms of IgA and play key roles in mucosal immunity as well as in the systemic circulation.

Structure and distribution: IgA exists in serum mainly as monomers, while in mucosal secretions it is typically found as dimers or polymers joined by a J chain. IgA1 has a relatively long hinge region rich in O-linked glycans, making it more flexible but more susceptible to proteases. IgA2 has a shorter hinge and is generally more resistant to bacterial proteases. In serum, IgA1 predominates (roughly 85–90%), whereas IgA2 is relatively enriched in secretions, particularly in gut-associated mucosa.

Secretory IgA and transport: Mucosal plasma cells secrete polymeric IgA that binds to the polymeric immunoglobulin receptor (pIgR) on epithelial cells. The IgA-pIgR complex is transcytosed to the luminal surface, where the secretory component of the receptor remains attached to form secretory IgA (SIgA). SIgA is adapted to survive proteolytic environments and plays a major role in immune exclusion, neutralizing pathogens and toxins at mucosal surfaces.

Genetics and regulation: The constant regions of IgA heavy chains are encoded by IGHA1 and IGHA2 genes on chromosome 6. Class switching to IgA is driven primarily by TGF-β. The two subclasses differ in glycosylation patterns and functional properties.

Clinical relevance: Aberrant IgA1 glycosylation can lead to immune complex formation implicated in IgA nephropathy. Selective IgA deficiency, the most common primary immunodeficiency, involves low IgA levels with variable clinical impact. IgA2’s protease resistance is considered advantageous for mucosal defense in the gut.