Immunoglobulins (
antibodies) frequently express constitutive functions. Two such functions are nucleophilic catalysis and the reversible binding to B-cell
superantigens. Constitutive or "naturally-occurring"
antibodies are produced spontaneously from germline genetic information. The antibody structural elements mediating the constitutive functions have originated over millions of years of phylogenic evolution, contrasting with
antigen-driven, somatic sequence diversification of the
complementarity determining regions (CDR) that underlies the better-known high affinity
antigen binding function of
antibodies. Often, the framework regions (FRs) play a dominant role in antibody constitutive functions.
Catalytic antibody subsets with promiscuous,
autoantigen-directed and microbe-directed specificities have been identified. Mucosal
antibodies may be specialized to express high-level catalytic activity against microbes transmitted by the mucosal route, exemplified by constitutive production of
IgA class
antibodies in mucosal secretions that catalyze the cleavage of HIV gp120. Catalytic specificity can be gained by constitutive noncovalent
superantigen binding at the FRs and by adaptive development of noncovalent classical
antigen or
superantigen binding, respectively, at the CDRs and FRs. Growing evidence suggests important functional roles for
catalytic antibodies in homeostasis,
autoimmune disease and protection against
infection. Adaptive antibody responses to microbial
superantigens are proscribed underphysiological circumstances. Covalent electrophilic immunogen binding to constitutively expressed nucleophilic sites in B-cell receptors bypasses the restriction on adaptive antibody production, and simultaneous occupancy of the CDR binding site by a stimulatory antigenic
epitope can also overcome the downregulatory effect of
superantigen binding at the FRs. These concepts may be useful for developing novel
vaccines that capitalize and improve on constitutive antibody functions for protection against microbes.