Faculty Bibliography

Hybrid resistance to a BALB/c plasmacytoma, MPC-11, has been investigated. The results indicate that heterozygosity within the H-2 complex is neither necessary nor sufficient for resistance to be observed. However, in the presence of a single gene or gene complex which segregates independently of H-2, differential effects of various H-2 haplotypes can be seen. Resistance is radiation-sensitive and silica-insensitive and probably depends on active immune responses. The data also suggest that production by a hybrid of endogenous viral antigens with certain type-specific determinants shared with viral antigens expressed on the tumor may interfere with resistance. The mechanism for this is not understood but might involve tolerance, suppression, or enhancing antibody

The secretory immune system of the mammary gland is undeveloped in virgin mice but becomes active at term and during lactation. This change appears to depend on migration to the mammary gland of precursors of IgA-secreting cells derived from the gut-associated lymphoid tissue, an origin which explains the specificity of milk IgA antibodies for enteric organisms. Because development of the epithelial components of the mammary gland is clearly under hormonal control, we examined the effect of mammotropic hormones on differentiation of the immune elements. Under a combined regimen of progesterone, estrogen, and prolactin, development of the glandular epithelium occurs with concomitant increments in the number of IgA-secreting plasma cells and amount of intraepithelial IgA. These increases appear to be due to enhanced capacity of the gland to attract or retain precursors of IgA plasma cells derived from gut-associated lymphoid tissue. Testosterone, which antagonizes lactation, also antagonizes development of the secretory immune system and decreases cellular trapping in the lactating gland. The ability of the gland to trap IgA immunoblasts is probably contingent upon a hormone-induced increase in receptors

1) Lymphoblasts in gut-associated lymphoid tissue, committed to the production of IgA, can home to the mammary glands of syngeneic mice and differentiate there into IgA-containing plasmablasts. The phenomenon is limited to near term and lactating recipients. 2) The ability of lymphocytes originating in gut-associated lymphoid tissue and sensitized to intestinal antigens to migrate to the mammary gland can account for the specificity of milk IgA toward intestinal microorganisms and the consequent passive protection offered to suckling infants. 3) The secretory immune system of the mammary gland is apparently under hormonal control since mammotropic hormones given to virgin females can induce morphological and functional characteristics seen naturally only during pregnancy and lactation. Examples are increased numbers of IgA plasma cells and the ability to trap their circulating precursors taken from mesenteric lymph nodes

Lymphoblasts from the mesenteric lymph nodes (MN) of mice home to the mammary glands of syngeneic recipients late in pregnancy and during lactation, and within hours of transfer most can be shown to contain IgA. Homing does not occur in virgins, in early pregnancy, or after weaning. Homing MN lymphoblasts are sensitive to antiserum to IgA plus complement, but not to other class-specific antisera. Thus, lymphoblasts in MN with the potential to home to the mammary gland are already committed to IgA synthesis and bear surface IgA before reaching their destination. These results explain observations, made by others, of specific IgA antibodies and IgA plasma cells in milk and colostrum after oral immunization. Under natural conditions it is likely that IgA precursor cells, after stimulation in the gut-associated lymphoid tissue by intestinal antigens, migrate to the mammary gland where they secrete antibodies which constitute an important defense mechanism of the newborn. In the absence of lactation, these cells probably form part of the normal traffic to the lamina propria of the small intestine

The fate of mesenteric lymph node lymphoblasts labeled with either [125I]iododeoxyuridine or [3H]thymidine can be studied after intravenous transfer into syngeneic mice both by measurement of radioactivity in various organs and by combined immunofluorescence and autoradiography of recipient tissues. Many of the lymphoblasts home to the lamina propria of the small intestine within hours of transfer; of these, many visibly secrete IgA. To determine whether the cells that will ultimately secrete IgA are already committed to IgA synthesis before their arrival in the gut, mesenteric lymph node cell populations were treated with various class-specific antisera to mouse immunoglobulins before transfer. Treatment with antiserum to IgA, plus complement, reduced the fraction of injected label recovered from the recipients' intestines, and also reduced the proportion of donor (labeled) cells containing IgA. We conclude that mesenteric lymph nodes are probably the principal source of IgA-secreting plasma cells in the lamina propria of the gut, and that the cells become committed to IgA synthesis and develop cell surface IgA before emigrating. This IgA is apparently synthesized by the cells that bear it since it is not removed by extensive rinsing at 37 degrees C, a maneuver that elutes passively adsorbed immunoglobulin