B Cell Differentiation and Immunoregulatory T Cell Function in Human Cord Blood Lymphocytes

Abstract

A B S T R A C T The functional maturity of T and B lymphocyte populations from human newborns was evaluated using a reverse hemolytic plaque assay to detect immunoglobulin-secreting cells generated in in vitro cultures stimulated with pokeweed mitogen (PWM), a T cell-dependent polyclonal activator, and the Epstein-Barr virus (EBV), a T cell-independent B cell activator. Cord blood lymphocytes failed to produce immunoglobulin in response to PWM, but did respond with immunoglobulin synthesis to stimulation with EBV. Co-culture experiments demonstrated that cord blood T cells would inhibit immunoglobulin production by adult cells stimulated with PWM, but not with EBV. Cord blood T cells did suppress immunoglobulin production by cord blood B cells when stimulated with a mixture of EBV and PWM, indicating that cord blood, in contrast to adult blood, contains a population of suppressor T cell precursors that are easily activated by PWM. Irradiation of the cord blood T cells with 2,000 rad eliminated the suppressor activity and revealed normal helper function for immunoglobulin (Ig) G, A, and M when these T cells were co-cultured with adult B cells. Cord blood B cells co-cultured with adult T cells or irradiated cord blood T cells did produce immunoglobulin in response to PWM, but the response was significantly lower than that of adult B cells, and only IgM was produced in these cultures. These studies demonstrate that both the T and B cells of the human newborn have significant functional differences compared with the functions of T and B lymphocyte populations in adults. INTRODUCTION The immune status of the human neonate has been the subject of intense investigation for many years.

Response of Human Newborn Lymphocytes to Alloantigen: Lack of Evidence for Suppression Induction

“…These studies did not exclude the possibility that suppression might develop primarily as a result of the mitogen activation of the newborn cells. Indeed, Tosato et al (25) finding that newborn T cells did not suppress adult lymphocyte responses to Epstein-Barr virus unless a mitogen was added, and our own observation of relatively low numbers of cells with the OKT 8+ suppressor phenotype in newborn blood (8) are consistent with the view that newborn T cells are not intrinsically suppressive, though they may become so as a result of mitogen activation. Lawler et 01.…”

Defective Production of Interleukin-6 by Monocytes: A Possible Mechanism Underlying Several Host Defense Deficiencies of Neonates

“…Specific defects include delayed maturation of B cells into antibody-producing cells (9)(10)(11)(12), deficient stimulation of T-cell maturation (1 3-15), and delayed induction of hematopoietic progenitor cell cycling (16). The clinical deficiencies resulting from these immature cellular processes include blunted synthesis of specific IgG (12,17,18) and delayed up-regulation of neutrophil production (19,20).…”

The capacity of interleukin-4 to inducein vitroIgE synthesis by B cells of patients with common variable immunodeficiency

“…Furthermore, it is clear that although the precise cascade of events leading to IgE production induced by IL-4 in vivo still remains to be determined, the frequency of successful IgE production in vitro by PBMC of patients with CVI is much lower than that by PBMC of healthy donors (2/8 versus 7/8), It remains to be clarified why PBMC of healthy donor 6 failed to produce IgE, but recent studies in our laboratory have indicated the PBMC of a small proportion of healthy donors do not produce IgE under the present culture conditions (Chretien et al, 1990), It has been shown that B cells of patients with CVI behave functionally like immature cord blood B cells (de Gast et al, 1980;Tosato e;Platts-Millse/a/,, 1981;Perreirae/a/,, 1982;Haber era/,, 1983;Brenner era/,, 1984;Mayer era/,, 1984), Stimulation of B cells of patients with CVI by EBV, PWM or supernatants of activated T cells results, as with cord blood B cells, predominantly in secretion of IgM and no or very low levels of IgA and IgG, However, we have found that cord blood cells from 8/8 donors produced IgE in the presence of IL-4, indicating that cord blood B cells and B cells of CVI patients differ in their capacity to produce IgE in response to unpublished). Therefore, B cells from patients with CVI cannot be compared functionally with cord blood B cells.…”