Maternal IgA Research Articles

Maternal IgG and IgA Antibodies Dampen Mucosal T Helper Cell Responses in Early Life

To maintain a symbiotic relationship between the host and its resident intestinal microbiota, appropriate mucosal Tcell responses to commensal antigens must be established. Mice acquire both IgG and IgA maternally; the former has primarily been implicated in passive immunity to pathogens while the latter mediates host-commensal mutualism. Here, we report the surprising observation that mice generate Tcell-independent and largely Toll-like receptor (TLR)-dependent IgG2b and IgG3 antibody responses against their gut microbiota. We demonstrate that maternal acquisition of these antibodies dampens mucosal T follicular helper responses and subsequent germinal center B cell responses following birth. This work reveals a feedback loop whereby Tcell-independent, TLR-dependent antibodies limit mucosal adaptive immune responses to newly acquired commensal antigens and uncovers a broader function for maternal IgG.

Does Circulating Antibody Play a Role in the Protection of Piglets against Porcine Epidemic Diarrhea Virus?

The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of concentrated serum antibody. Piglets were orally inoculated with PEDV (USA/IN/2013/19338E, 1 x 103 TCID50 per piglet) 24 hours later and then monitored for 14 days. Piglets remained with their dam throughout the experiment. Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body weight, and body temperature were collected daily. Fecal samples were tested by PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for the effects of systemic PEDV antibody levels on growth, body temperature, fecal shedding, survival, and antibody response. The analysis showed that circulating antibody partially ameliorated the effect of PEDV infection. Specifically, antibody-positive groups returned to normal body temperature faster and demonstrated a higher rate of survivability than piglets without PEDV antibody. When combined with previous literature on PEDV, it can be concluded that both systemic antibodies and maternal secretory IgA in milk contribute to the protection of the neonatal pig against PEDV infections. Overall, the results of this experiment suggested that passively administered circulating antibodies contributed to the protection of neonatal piglets against PEDV infection.

Clinically significant anti-KEL RBC alloantibodies are transferred by breast milk in a murine model.

Fetuses affected by maternal RBC alloantibodies may have prolonged anaemia after birth, leading one to question whether maternal alloantibody transfer may occur outside the placenta. In response to a recent publication describing breast milk transfer of clinically significant amounts of maternal antiplatelet IgA antibodies from mother to nursing infant, we hypothesized that maternal RBC alloantibodies may also be capable of being transferred in breast milk. The presence and clinical significance of breast milk alloantibody transfer were tested through a series of pregnancy, fostering and transfusion experiments, using a murine model in which transgenic RBCs express the human KEL glycoprotein. Maternal anti-KEL immunoglobulins, induced through transfusion or pregnancy, were detected in the aqueous phase of breast milk. Further, efficient transfer of maternal anti-KEL IgG and IgA to nursing pups was observed in fostering experiments. The breast milk-acquired alloantibodies were clinically significant in wild-type pups in a transfusion setting, binding to 'incompatible' KEL RBCs and leading to premature clearance from the circulation. Although breast milk-acquired alloantibodies also bound to the RBCs of transgenic KEL-positive fostered pups, no anaemia resulted. Taking these murine data in combination with recently published human data of maternal antiplatelet IgA antibodies in breast milk leading to sequelae in some infants, it is theoretically possible that maternal anti-RBC IgA alloantibodies may also be transferred in human breast milk and may lead to sequelae in some infants under some circumstances.

Passive acquisition of anti-Staphylococcus aureus antibodies by newborns via transplacental transfer and breastfeeding, regardless of maternal colonization

OBJECTIVE:To investigate the transmission of anti-Staphylococcus aureus (Sa) IgG, IgG1 and IgG2 via placental transfer and the transfer of IgA via the colostrum according to maternal Sa carrier status at delivery.METHODS:We evaluated anti-Sa IgG, IgG1 and IgG2 in maternal and cord sera and IgA in colostrum from a case (n=49, Sa+) and a control group (n=98, Sa-).RESULTS:Of the 250 parturients analyzed for this study, 49 were nasally colonized with S. aureus (prevalence of 19.6%). Ninety-eight non-colonized subjects were selected for the control group. The anti-Sa IgG, IgG1 and IgG2 levels and the IgG avidity indexes in the maternal and cord sera did not differ between the groups, with a low transfer ratio of anti-Sa IgG to the newborns in both groups. The anti-Sa IgG2 titers were significantly higher than the IgG1 titers in the maternal and cord sera. Inversely, the transfer ratios were higher for anti-Sa IgG1 compared with IgG2; however, no differences between the groups were detected. The Sa-specific IgA levels and avidity indexes in the colostrum were equivalent between groups.CONCLUSIONS:Maternal Sa nasal colonization at delivery is not associated with higher antibody levels in the mother or newborns. The high titers of anti-Sa IgG2 found in the cord serum indicate a greater reactivity with non-protein antigens, which may further contribute to the susceptibility to staphylococcal infections at birth. The presence of IgA in the colostrum with avidity to S. aureus reinforces the importance of breastfeeding shortly after birth.

TLR-dependent anti-commensal antibodies regulate intestinal immune homeostasis (MUC9P.750)

Abstract Maternal antibodies have been suggested to be important for establishing intestinal immune homeostasis in developing offspring, yet the mechanisms by which maternal antibodies achieve this remain unclear. We analyzed the gut immune response in mice born to antibody-deficient dams and found that maternal antibodies regulate the activation of mucosal CD4+ T cells. Interestingly, maternal IgA, the dominant mucosal antibody isotype, was not necessary for this regulation. As such, we developed an unbiased flow cytometric based assay to assess the microbiota-specific antibody response, thereby allowing us to investigate if other antibody isotypes are important for enforcing intestinal immune homeostasis. Unexpectedly, we found that mice generate a robust anti-commensal IgG2b- and IgG3- response. This commensal-specific IgG response occurs through a pathway independent of T cells, yet dependent on signaling through TLR2 and TLR4. These TLR-dependent anti-commensal IgG antibodies are transmitted from mothers to their offspring. There, they function to regulate T follicular helper responses and subsequently dampen germinal center B cell responses. This work reveals a feedback loop whereby T cell-independent antibody responses function to regulate mucosal CD4+ T cell responses and thereby establish equilibrium between the host and its resident microbiota.

Role of Maternal Elimination Diets and Human Milk IgA in the Development of Cow's Milk Allergy in the Infants.

KM Jarvinen, JE Westfall, MS Seppo. Clin Exp Allergy. 2014;44(1):69–78 The goal of this study was to evaluate the association of maternal cow’s milk (CM) avoidance during breastfeeding with specific IgA levels in human milk and the development of CM allergy in infants. This prospective birth cohort study evaluated 145 mother–infant pairs who were recruited at birth and followed up prospectively at 0 to 2 weeks and at 1, 3, 6, 12, and 18 months to determine development of food allergy in the infants. Infants were all term and classified into 2 groups: high risk because of sibling(s) with food allergy and low risk, defined as having only nonatopic first-degree relatives. …

Role of goblet cells and mucin layer in protecting maternal IgA in precocious birds

Immune protection of the gut in early life depends on provision of maternal antibodies, particularly that of IgA. In precocial birds (in this study Gallus gallus domesticus) the egg provides the only source of maternal antibodies, IgA inclusive. The gut-life of IgA in hatchlings is expected to be brief due to antigen binding and intestinal washout, and maternal IgA is likely to be depleted prior to immune independence at 7–10days of age in the domestic fowl. We followed the track of maternal IgA in mucosal surfaces of the fowl and describe for the first time a mechanism that might provide the means to extend the active period of maternal IgA in the gut. Maternal IgA was located in the gut, lung, and cloacal bursa in embryos and hatchlings prior to the appearance of endogenic IgA positive plasma cells (D3 in the bursa or D7 in the gut and lung); the source of IgA was most probably the yolk, as the plasma was devoid of IgA till D7 post-hatch. The levels of maternal IgA decreased with time, but were still easily determined at the onset of endogenous IgA production following maturation of the adaptive immune system. Persistence of maternal IgA in the gut was enabled by goblet cell up-take by a yet un-described mechanism, and its consequent release in a mucin-like layer on enterocyte apical surfaces.

Role of maternal elimination diets and human milk IgA in the development of cow's milk allergy in the infants

The role of maternal avoidance diets in the prevention of food allergies is currently under debate. Little is known regarding the effects of such diets on human milk (HM) composition or induction of infant humoral responses. To assess the association of maternal cow's milk (CM) avoidance during breastfeeding with specific IgA levels in HM and development of cow's milk allergy (CMA) in infants. We utilized HM and infant serum samples from a prospective birth cohort of 145 dyads. Maternal serum and HM samples were assessed for casein and beta-lactoglobulin (BLG)-specific IgA and IgG by ELISA; 21 mothers prophylactically initiated a strict maternal CM avoidance diet due to a sibling's history of food allergy and 16 due to atopic eczema or regurgitation/vomiting seen in their infants within the first 3 months of life. Infants' sera were assessed for casein and BLG-specific IgG, IgA and IgE; CMA was confirmed by an oral food challenge. The impact of HM on BLG uptake was assessed in transcytosis assays utilizing Caco-2 intestinal epithelial cell line. Mothers avoiding CM had lower casein- and BLG-specific IgA in HM than mothers with no CM restriction (P = 0.019 and P = 0.047). Their infants had lower serum casein- and BLG-specific IgG(1) (P = 0.025 and P < 0.001) and BLG-specific IgG(4) levels (P = 0.037), and their casein- and BLG-specific IgA levels were less often detectable than those with no CM elimination diet (P = 0.003 and P = 0.007). Lower CM-specific IgG4 and IgA levels in turn were associated with infant CMA. Transcytosis of BLG was impaired by HM with high, but not low levels of specific IgA. Maternal CM avoidance was associated with lower levels of mucosal-specific IgA levels and the development of CMA in infants. HM IgA may play a role in preventing excessive, uncontrolled food antigen uptake in the gut lumen and thereby in the prevention of CMA.

Maternal antibodies enhance systemic and local immune responses after early mucosal immunization in a porcine model

Event Abstract Back to Event Maternal antibodies enhance systemic and local immune responses after early mucosal immunization in a porcine model Edgar R. Guzman-Bautista1, Carlos E. Garcia-Ruiz2, Alicia L. Gama2, Carmen Ramirez-Estudillo1, Oscar I. Rojas1 and Marco A. Vega-Lopez1* 1 CINVESTAV-IPN, Infectomics and Molecular Pathogenesis, Mexico 2 Universidad Nacional Autonoma de Mexico, Facultad de Estudios Superiores Cuautitlan, Mexico In newborn mammals, maternal antibodies (MatAb) confer protection against antigenic challenges, although it has been also reported a suppressive effect on neonatal immune response to immunization (1, 2). We evaluated the immune response to ovoalbumin (OVA) after mucosal immunization on 7 and 14 days (7d, 14d) old SPF Vietnamese minipigs from negative (OVA-) or previously immunized (OVA+) sows. Sows were intramuscularly immunized to OVA 30 days before farrowing. Maternal anti-OVA IgG and IgA were detected in colostrum and serum and were intestinally absorbed by the offspring during the first three days of life. These antibodies were detected in piglets’ serum, but not in mucosal secretions (saliva, nasal secretion). The own systemic (serum) anti-OVA IgG and IgA responses were significantly higher in piglets immunized at 7d of life, from OVA+ sows, compared with piglets from OVA- sows (figure 1A) and similar to piglets immunized at 14d of age. Also the own anti-OVA IgA response in nasal secretion was higher in OVA+ 7d piglets (figure 1B) and in saliva of OVA+ 14d piglets (not shown). This specific immune response lasted far beyond MatAb halflife. In our hands, the systemic suppressive effect of MatAb, reported by others at early immunization, was not detected. On the contrary, a stimulating effect was found with MatAb in one week old immunized piglets, both in systemic and mucosal compartments and this effect disappeared in 14d old immunized piglets. Ag specific maternal factors (anti-Id Ab?) (3) may positively favor the immune response in immature young animals. These results open the possibility to induce effective early systemic and mucosal immune responses in the young through immunization, even in the presence of MatAb. Figure 1. Serum IgG (A) and nasal IgA (B) anti-ovoalbumin (OVA) antibodies in piglets immunized at 7 days old receiving maternal antibodies (black squares, OVA+ sow) or not (white squares, OVA- sow). Piglets were subcutaneously (SC) immunized twice (days 0 and 10) and intranasally boosted (days 20 and 55) with OVA. Each point is the average of 6 (OVA+) or 5 (OVA-) pigs +/- SEM. Unpaired t-test *P<0.05, **P<0.01, ***P<0.001. Scales graphs have different units. Figure 1 Acknowledgements Supported by grants from CONACyT (234097) and ICyTDF (323/09), Mexico. Thanks to DVM Manuel Flores and Daniel Cortes for technical assistance. References

Lectin-based analysis of fucose and sialic acid expressions on human amniotic IgA during normal pregnancy

The sugar moiety of IgA is known to provide a link between the innate and adaptive immune systems. Terminally located glycotopes on IgA are potential ligands engaged in the interactions which may modulate the biological activities of IgA. In the present work the expressions of Maackia amurensis (MAA), Sambucus nigra (SNA), Lens culinaris (LCA), Tetragonolobus purpureus (LTA), and Ulex europaeus (UEA) reactive glycotopes on maternal plasma and amniotic IgA were evaluated in relation to the progression of a normal human pregnancy, from the 2nd trimester, throughout the 3rd trimester, perinatal period, post-date pregnancy and delivery, by lectin-IgA-ELISA, using specific biotinylated lectins. The amniotic and maternal plasma IgA concentrations and a degree of SNA and LCA reactivity of maternal plasma IgA were almost unaltered during the normal pregnancy. The amniotic IgA from the 2nd trimester was decorated by MAA-, SNA-reactive and LCA-, LTA-, and UEA-reactive glycotopes. At the turn of the 2nd and 3rd trimesters the expression of MAA-, SNA-, LTA-, and UEA-reactive glycotopes, except for LCA-reactive, increased and remained almost at unaltered levels throughout the perinatal period and delivery. However, in the post-date pregnancy the expression of LCA-, LTA-, and UEA-reactive and SNA-reactive glycotopes were significantly higher. The unique fucosylated and sialylated glycovariants of amniotic IgA associated with the progression of the normal pregnancy may illustrate a general importance of carbohydrate-lectin receptor interactions in the control and modulation of biological events to ensuring homeostasis during pregnancy, protection and well-being of fetus.

495 Maternal and Endogenous Iga Protection in Infants with Respiratory Tract Infections

BackgroundIntestinal Ig A protection in infants relies both on maternal human milk sIgA (secretory immunoglobulin A) controlled by chemokines like CCL28, with roles of amplifying mammary secretion and passive gut...

Serum immunoglobulin A concentration in infancy, but not human milk immunoglobulin A, is associated with subsequent atopic manifestations in children and adolescents: a 20‐year prospective follow‐up study

Serum and secretory IgA concentrations have been suggested to be inversely associated with allergic symptoms in children. Furthermore, low maternal milk IgA concentration has been suggested to be associated with the development of cow's milk allergy. Our aim was to explore whether the serum IgA concentrations in infancy and the IgA concentration of maternal milk predict atopic manifestations in childhood and up to age 20 years. A cohort of 200 unselected full-term newborns was prospectively followed up from birth to age 20 years with measurement of serum total IgA at ages 2 and 6 months. The mothers were encouraged to maintain exclusive breastfeeding for as long as possible. Total IgA concentration of maternal milk was measured at birth (colostrum, n=169) and at 2 (n=167) and 6 (n=119) months of lactation. The children were re-assessed at ages 5, 11 and 20 years for the occurrence of allergic symptoms, with skin prick testing and measurement of serum IgE. Children and adolescents with respiratory allergic symptoms and sensitization had a higher serum IgA concentration at age 2 months than the non-atopic subjects. Colostrum and breast milk IgA concentrations were not associated with the development of allergic symptoms in the recipient infant. However, maternal milk IgA concentration at 6 months of lactation was inversely associated with elevated serum total IgE and positive skin prick test to tree pollen in the offspring at age 20 years. Increased serum IgA concentration at age 2 months is associated with the development of subsequent allergic symptoms and sensitization in childhood and adolescence. Maternal milk IgA concentrations are not associated with subsequent allergic symptoms in the recipient infant. The present study provides novel information on the role of IgA in the development of respiratory allergy and sensitization.

Effects of supplemental β-carotene with whey on IgA transfer from maternal milk and mucosal IgA induction in neonatal mice and calves

Data from 17 pregnant mice and 33 Japanese Black calves were collected to clarify the effect of supplemental β-carotene with whey on IgA transfer from maternal milk and mucosal IgA induction in neonatal mice and calves. Dietary treatments in milk replacers were 1) 26% CP as in skim milk (control), 2) 26% CP as whey and 3) 26% CP as whey and 30mg/kg β-carotene. Diets were offered from 6.5days postcoitus to 14days postpartum in pregnant mice and from 3 to 63days postpartum in calves. Supplemental β-carotene with whey increased the numbers of IgA antibody secreting cells (ASC) in the mammary gland in maternal mice and IgA concentration in stomach contents in neonatal mice at 14days postpartum, which was the consequence of the higher IgA transfer from maternal milk to neonates. The number of IgA ASC in the mammary gland in maternal mice fed whey was higher than that of control mice, but intestinal IgA concentration of neonatal mice was not affected by treatments. Supplemental β-carotene with whey drastically increased serum β-carotene concentration in calves at 14 and 42days postpartum. Supplemental β-carotene with whey had no effects on fecal IgA concentration and fecal water in calves. These results suggest that β-carotene supplementation with whey to maternal mice during pregnancy and lactation enhances IgA transfer from maternal milk to neonates, but supplemental β-carotene has little effect on mucosal IgA induction in neonatal mice and calves.

Long‐term shedding of hepatitis E virus in the feces of pigs infected naturally, born to sows with and without maternal antibodies

Pigs are presumed reservoirs for hepatitis E virus (HEV) transmission to humans. To examine infection kinetics, two litters of domestic pigs (A and B, each containing 10 piglets) infected naturally with HEV were studied until pigs were 6 months old. Maternal IgG and IgA antibodies were detected in litter A piglets, but not in litter B ones. All pigs shed HEV in feces when they were 30-110 days old, and 17 developed viremia at 40-100 days of age. Phylogenetic analysis revealed a highly close sequence of HEV genotype 3 in all pigs. The serum levels of specific IgG and IgA were similar in all pigs, although IgA was not detected in the feces. Interestingly, the onset of both viremia and seroconversion was delayed significantly in litter A pigs. The kinetics of fecal virus shedding was similar in both litters; shedding was not detected after the pigs were 120 days old. The differences in the infection kinetics between litters A and B suggested that maternal antibodies delayed the onset of viremia and seroconversion. Quantitative real-time reverse transcriptase-polymerase chain reaction revealed that HEV RNA in feces peaked 10 days after initial shedding of approximately 10(6.0) copies/g. The viral load was much lower in the serum than in the feces. At 200 days of age, HEV RNA was found in the internal organs of 3 out of 13 pigs. These study findings improve the understanding of the dynamics of natural HEV transmission in pigs, which could help in controlling virus transmission from pigs to humans.

P13-03. Neutralizing antibody to HIV-1 Env from hyperimmune bovine colostrum as a mucosal microbicide strategy for preventing virus transmission

Background Newborn mammals derive passive mucosal and systemic immunity against pathogens from the mothers' first milk (colostrum). Bovine colostrum contains antiviral proteins, such as lactoferrin and high levels of maternal IgG, IgM and IgA that are actively concentrated from serum before birth. Immunising cows with HIV-1 Env gp140 oligomers during pregnancy offers a strategy for preparing highly concentrated antibodies (Abs) with HIV-1 neutralizing activity. In this study we develop HIV immune bovine colostrum derived polyclonal antibodies. We examine whether these might match the protective properties of neutralizing monoclonal-Abs.

Two secretory immune systems (mucosal and barrier) in human intrauterine development, normal and pathological (Review)

The role of protein components of the secretory immune system (SIS), such as the polymeric immunoglobulin receptor/secretory component (pIgR/SC), immunoglobulins (Igs) and joining (J) chain, in human intrauterine development was reviewed. These components are already present in 3.5- to 4-week-old embryos, and found in all tissues and organs of epithelial origin. The SIS is made up of two parts: the SIS of mucous membranes and their derivatives (mucosal or secretory immune system), and the SIS of barrier structures (barrier immune system). During organogenesis, SC disappears from the cells of organs that lose their exocrine Ig-secretion function, such as the hypophysis, pancreatic islands and adrenal glands. In cells and tissues of mesenchymal origin, SC is absent from the start, i.e. during their initial development. As examples of the barrier immune system, blood-tissue and tissue-tissue barriers, such as the chorion of the placenta, the epithelium of the choroid plexuses in the brain, as well as other barrier structures to Ig transfer were considered. Besides the SC and J chain, Fc receptors, cellular and tissue structures participate in this process. Three stages were described in Ig transfer: i) passing from the maternal blood into intervillous spaces and the trophoblast, ii) shifting in the intravillous stroma and its cells, and iii) excretion into embryonic (fetal) blood through the endothelium of the trophoblastic villous capillaries. Igs of maternal origin, mainly IgG and least abundant IgA, pass through the placental barrier in healthy embryos. Following a massive antigenic attack, the increased exocrine secretion of IgG, IgA, and IgM to a lesser extent, are already seen in embryos, reflecting increased functional activity of the SIS. Thus, in human intrauterine development, the SIS is a very early immune defensive system, which presents and acts before the appearance of the common lymphoid system.

Development of Intestinal Microbiota in Mice and Its Possible Interaction with the Evolution of Luminal IgA in the Intestine

The development of the intestinal microbiota and the evolution of the fecal IgA in mice were analyzed from 18 to 40 days old by PCR temperature gradient gel electrophoresis (TGGE) and ELISA, respectively. There were two events for the diversification of the intestinal microbiota from suckling to maturity. The first change occurred between days 21 and 22 after birth, when the diversity of the intestinal microbiota showed a remarkable increase at this time. The second change occurred from days 27 to 30 after birth, and the increase in the diversity of the intestinal microbiota ceased. The amount of fecal IgA decreased from days 18 to 20, remained low until day 22, on day 23, it recovered and then continued to increase. This study suggests that there are possible interactions between the development of intestinal microbiota and the evolution of intestinal secretion of IgA in mice, the same as in rats, although the second change in mice intestinal microbiota occurred a few days later than in rats. The decline in maternal IgA supply as the suckling period proceeded presumably allowed the bacterial colonization. As a consequence of this increase in bacterial colonization, the secretion of the self-SIgA was accelerated in the pups.

Development of the intestinal microbiota in rats and its possible interactions with the evolution of the luminal IgA in the intestine

The development of the intestinal microbiota in rats from 18 to 40 days old was analyzed by monitoring 16S ribosomal DNA diversity in fecal samples by polymerase chain reaction temperature gradient gel electrophoresis (PCR-TGGE) combined with hierarchical clustering analysis. The evolution of the fecal IgA was also analyzed by an additional experiment. There were two events for the diversification of the intestinal microbiota from suckling to maturity. The first change occurred between days 21 and 22 after birth, and the diversity showed a remarkable increase at this time. The second change occurred from days 24 to 27, and the increase in the diversity of the intestinal microbiota ceased. The amount of fecal IgA decreased from days 18 to 22 and remained low until day 24. On day 27, it recovered and continued to increase. This study suggests the possible interactions between the development of the intestinal microbiota and the evolution of the intestinal SIgA. The decline in maternal IgA supply as the suckling period proceeded allowed the bacterial colonization. As a consequence of this increase in bacterial colonization, the secretion of the self-SIgA was accelerated in pups.

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of human immunodeficiency virus infection in Ugandan infants

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of human immunodeficiency virus infection in Ugandan infants

Delayed anti-kappa response in kappa-deficient mice after neonatal, oral immunization with kappa-containing IgG

Antibody responses to kappa (κ)-light (L) chain are absent in normal (Cκ+/+) animals because of tolerance due to the abundance of κ-L chains expressed on more than 95% of all B cells and serum Ig. When heterozygous κ-sufficient (Cκ+/−) females are bred with homozygous κ-deficient (Cκ−/−) males, half of their offspring will become κ-deficient but have received κ-L chain containing maternal Ig, mainly IgG and IgA, through placental and intestinal transmission. The κ-containing maternal Ig persists for more than 2 months in the circulation of the offspring. Starting from weeks 15 to 20 of age, a spontaneous antibody response towards the maternal κ-L chains can be recorded. The time of onset, as well as the magnitude of the responses differ among individuals of the same litter. Invariably, once a response has been initiated, it transits into an IgG-type of response, which upon injection with κ-containing protein shows the features of a secondary type of immune response.