Natural Polyreactive IgA and IgM Autoantibodies in Human Colostrum

Abstract

Secretory antibodies against bacteria and viruses in human colostrum and milk are known to be important protective factors for the breast-fed infant. The authors have shown by enzyme immunoassay that colostrum contains IgA and IgM antibodies to a number of autoantigens: native DNA, actin, myosin, myoglobin, laminin, transferrin and thyroglobulin. These antibodies were polyspecific-those with anti-DNA reactivity immunopurified on a DNA-cellulose affinity column bound to a panel of self- and environmental antigens. The levels of natural autoantibodies in the immunoglobulin fraction of human colostrum were 3-10 times lower (when presented as antibody activity per microgram of immunoglobulin) than in the immunoglobulin fraction of serum. The biological significance of the presence of B cells with autoantibody specificity in the mammary gland and of natural autoantibodies in colostrum and milk is not clear. It has been suggested that self-reacting autoantibodies in serum play a major role in the selection of the pre-immune B-cell repertoire and in the maintenance of the immune homeostasis. The authors hypothesize that the natural autoantibodies in colostrum and milk may contribute to the selection process of physiological repertoire during the early postnatal period in breast-fed infants. This could explain the lower frequency of allergic, inflammatory and autoimmune diseases and lymphomas which is seen in their later life when compared with that observed in children who have been formula-fed after birth.

Tumor-Associated and Disease-Associated Autoantibody Repertoires in Healthy Colostrum and Maternal and Newborn Cord Sera

“…The functions of these and other autoantibodies to tumor-associated and other selfAgs in healthy mothers and newborns need to be studied. It would be important to know whether the T cell repertoire in healthy subjects-the T cell homunculus-likewise contains clones potentially reactive to these particular self-Ags (23). In any case, the prevalence of highly reactive autoantibodies to tumor-associated self-Ags supports the idea that the healthy immune system is outfitted, even from birth, to express some form of tumor-associated immune reactivity.…”

“…Compatible with maternal transfer, the only isotype of these Abs detected in cord sera was IgG-IgM and IgA Abs to these Ags were found only in maternal sera. Note that some of the viral and bacterial Ags highly reactive with serum Abs were less reactive with milk Abs; thus, systemic and secretory immunization appear to differ (19)(20)(21)(22)(23).…”

Natural Antibodies to CCR5 from Breast Milk Block Infection of Macrophages and Dendritic Cells with Primary R5-Tropic HIV-1

“…We purified the Abs to CCR5 from pooled breast milk of both HIV-seropositive and -seronegative women by means of affinity chromatography on a synthetic peptide corresponding to a 20-amino acid region (II.E/C-CCR5) derived from the second extracellular loop of CCR5. This loop together with the N-terminal sequence (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and the first extracellular loop (aa 89 -102) is involved in the binding of gp120 and of natural CCR5 ligands to the CCR5 molecule (6,(11)(12)(13). We focused on the second extracellular loop of CCR5 that was shown to be immunogenic and induce a B and T cell response.…”

“…Breast milk contains high amounts of immunoglobulins, predominantly of the secretory IgA (sIgA) 4 and to a lesser degree of the IgG and sIgM isotypes that are produced in the absence of deliberate immunization and independently of exposure to Ags. Most natural Abs in the breast milk of healthy women are self-reactive Abs (9,10).…”

Infection of Macrophages and Dendritic Cells with Primary R5-Tropic Human Immunodeficiency Virus Type 1 Inhibited by Natural Polyreactive Anti-CCR5 Antibodies Purified from Cervicovaginal Secretions

“…A pathological role for NAbs has been suggested in autoimmunity, tumor cell recognition, and atherosclerosis (3,9,20). It has been shown that human colostrum and saliva contain large amounts of S-IgA polyreactive NAbs (44). The natural humoral immunity of the female genital tract, however, has not yet been studied.…”